Nervous System I Test 4 Drugs

CNS STIMULANT FOR ADHD

MOA: GREATLY INCREASES NE, AND SOMEWHAT DA EFFLUX IN THE PRE-FRONTAL CORTEX TO ENHANCE PRE-FRONTAL COGNITIVE FUNCTION. IT DOES THIS WHILE ONLY SLIGHTLY INCREASING DA GOING TO THE NUCLEUS ACCUMBENS (THE PLEASURE AREA) TO DECREASE (THOUGH NOT ELIMINATE) CHANCE OF ADDICTIVE PROPERTIES.

IMMEDIATE RELEASE HAS 3-4 HRS OF DURATION

RITALIN, METADATE, CONCERTA, FOCALIN(DEXTROMETHYLPHENIDATE), DAYTRANA

CNS STIMULANT FOR ADHD

MOA: AMPHETAMINES PROMOTE RELEASE OF CATECHOLAMINES (NE, DA) FROM THEIR PRE-SYNAPTIC VESICLES INTO THE SYNAPTIC CLEFT TO ACT ON POST-SYNAPTIC RECEPTORS. THEY CAN ALSO BLOCK CATECHOLAMINE REUPTAKE INTO THE PRE-SYNAPTIC CELL BY BLOCKING NET OR DAT.

IMMEDIATE RELEASE HAS 4-5 HR DURATION

DEXEDRINE, DEXTROSTAT, ADDERALL

NE UPTAKE INHIBITOR FOR ADHD

MOA: BY BLOCKING NE REUPTAKE INTO THE PRE-SYNAPTIC CELL, NE IS LEFT OUT IN THE SYNAPTIC CLEFT LONGER TO ACT ON POST-SYNAPTIC RECEPTORS DELIVERING SYMPATHETIC RESPONSE.

STRATTERA

• ALPHA 2 AGONIST FOR ADHD OR HTN
• NOT A CNS STIMULANT!

MOA FOR ADHD: ACTS AS AN ALPHA 2 AGONIST AT POST-SYNAPTIC ADRENERGIC RECEPTORS IN THE PRE-FRONTAL CORTEX, WHICH THEORETICALLY IMPROVES DELAY RELATED FIRING OF PREFRONTAL CORTEX NEURONS, RESULTING IN BETTER WORKING MEMORY AND BEHAVIORAL INHIBITION.

TENEX, INTUNIV

• GENERAL ANESTHETIC
• INHALATION
• HALOGENATED

FLUOTHANE

• GENERAL ANESTHETIC
• INHALATION
• HALOGENATED

FORANE

• GENERAL ANESTHETIC
• INHALATION
• HALOGENATED

ETHRANE

• GENERAL ANESTHETIC
• INHALATION
• HALOGENATED

SUPRANE

• GENERAL ANESTHETIC
• INHALATION
• HALOGENATED

ULTANE

• GENERAL ANESTHETIC
• INHALED

NO BRAND NAME

• GENERAL ANESTHETIC
• PARENTERAL

DIPRIVAN

• GENERAL ANESTHETIC
• PARENTERAL

LUSEDRA

• GENERAL ANESTHETIC
• PARENTERAL

AMIDATE

• GENERAL ANESTHETIC
• PARENTERAL

KETALAR

BARBITURATE

• GENERAL ANESTHETIC
• PARENTERAL

MOA:

-BINDS BARB SITE ON ALPHA SUBUNIT OF GABAa RECEPTORS TO INDUCE HYPERPOLARIZATION AND RELAXATION.

PENTOTHAL

LOCAL ANESTHETIC

NET INHIBITOR

INCREASES SYMPATHETIC RESPONSE BY INHIBITING NE REUPTAKE BACK INTO PRE-SYNAPTIC CELLS, AND ALSO PUSHES NE IN PRE-SYNAPTIC VESICLE INTO SYNAPSE TO ACT ON ADRENERGIC RECEPTORS

WOULD PROBABLY BE THE ONLY WAY TO STAY AWAKE LONG ENOUGH TO GET THROUGH ALL THE MATERIAL FOR THESE TESTS

LOCAL ANESTHETIC

XYLOCAINE

LOCAL ANESTHETIC

NOVACAIN

LOCAL ANESTHETIC

PONTOCAINE

LOCAL ANESTHETIC

MARCAINE

1.BDZ-1(w1) BINDING SITE BETWEEN THE a1 AND y SUBUNITS ON GABA-A RECEPTORS, NOTE THE B SUBUNIT IS ALSO REQUIRED FOR ACTIVITY

2.BDZ-2(w2) BINDING SITE BETWEEN THE a2 AND y SUBUNITS ON GABA-A RECEPTORS, NOTE THE B SUBUNIT IS ALSO REQUIRED FOR ACTIVITY

THIS IS THE PRIMARY DIFFERENCE BETWEEN YOUR ANXIETY VERSUS INSOMNIA BENZODIAZEPINES!

BENZODIAZEPINE FOR ANXIETY

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-2 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

INTERMEDIATE 1/2 LIFE (6-24 HRS BUT AVERAGES A LITTLE UNDER 12 HRS)

NOTE THAT ALTHOUGH BOTH BENZOS AND BARBS GENERALLY DECREASE MOST FUNCTIONS, INCLUDING BP, BENZOS ACTUALLY 'INCREASE' HEART RATE AT PRE-ANESTHETIC DOSES.

XANAX

BENZODIAZEPINE FOR ANXIETY

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-2 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

LIBRIUM

BENZODIAZEPINE FOR ANXIETY

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-2 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

ACTIVE METABOLITE IS CREATED IN GASTRIC JUICES FOR THIS PARTICULAR BENZO

TRANXENE

BENZODIAZEPINE FOR ANXIETY/SEIZURES

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-2 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

VALIUM

BENZODIAZEPAM FOR ANXIETY/SEIZURES

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-2 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

ATIVAN

BENZODIAZEPINE FOR ANXIETY

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-2 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

SERAX

BENZODIAZEPINE FOR ANXIETY/SEIZURE

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-2 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

KLONOPIN

• 1.BDZ-1(w1) BINDING SITE BETWEEN THE a1 AND y SUBUNITS ON GABA-A RECEPTORS, NOTE THE B SUBUNIT IS ALSO REQUIRED FOR ACTIVITY
• 2.BDZ-2(w2) BINDING SITE BETWEEN THE a2 AND y SUBUNITS ON GABA-A RECEPTORS, NOTE THE B SUBUNIT IS ALSO REQUIRED FOR ACTIVITY

THIS IS THE PRIMARY DIFFERENCE BETWEEN YOUR ANXIETY VERSUS INSOMNIA BENZODIAZEPINES!

BENZODIAZEPINE FOR INSOMNIA

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

INTERMEDIATE 1/2 LIFE (6-24 HRS)

PROSOM

BENZODIAZEPINE FOR INSOMNIA

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

LONG 1/2 LIFE (>24 HRS)

NIGHTMARES ARE A NOTED SIDE EFFECT OF FLURAZEPAM! PEOPLE ON ELM ST SHOULD NOT TAKE THIS.

DALMANE

• BENZODIAZEPINE FOR INSOMNIA
• USED MOSTLY FOR "TWILIGHT" ANESTHESIA

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

SHORT 1/2 LIFE < 6 HRS

VERSED

BENZODIAZEPINE FOR INSOMNIA

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

LONG 1/2 LIFE (>24 HRS)

DORAL

BENZODIAZEPINE FOR INSOMNIA

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

INTERMEDIATE 1/2 LIFE (6-24 HRS)

RESTORIL

BENZODIAZEPINE FOR INSOMNIA

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

SHORT 1/2 LIFE < 6 HRS

HALCION

BENZODIAZEPINE ANTAGONIST

IV ONLY, FOR REVERSAL OF SEDATIVE EFFECTS BY BENZOS AFTER OVERDOSE; THOUGH THIS REVERSAL DOES NOT WORK WITH BARBITUATES, TCAs, OR OPIOIDS

MOA: COMPETITIVE INHIBITION OF BENZO SITES ON GABAa RECEPTORS

LASTS 1/2 TO 1 HR; CAN CAUSE SEIZURES, WHICH IS LOGICAL CONSIDERING BENZOS TEND TO BE ANTI-EPILEPTICS, SO IF YOU BLOCK THE BENZO SITE OF ACTION TO A GREAT DEGREE YOU COULD CAUSE SEIZURES

ROMAZICON

NOVEL BENZODIAZIPINE FOR SHORT TERM INSOMNIA RELIEF W/ LITTLE EFFECT ON SLEEP STAGES

MOA: SELECTIVE FOR BZD-1 a1 SUBUNIT ON GABAa

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

LUNESTA

• 1/2 LIFE 6 HRS
• INFREQUENT TOLERANCE OR DEPENDANCE

NOVEL BENZODIAZIPINE FOR SHORT TERM INSOMNIA RELIEF; IMMEDIATE USE AT BEDTIME! LITTLE EFFECT ON SLEEP STAGES

MOA: SELECTIVE FOR BZD-1 a1 SUBUNIT ON GABAa

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

SONATA

• 1/2 LIFE 1 HR
• INFREQUENT TOLERANCE OR DEPENDANCE

NOVEL BENZODIAZEPINE FOR SHORT TERM INSOMNIA RELIEF W/ LITTLE EFFECT ON SLEEP STAGES

MOA: SELECTIVE FOR BZD-1 a1 SUBUNIT ON GABAa RECEPTORS

• MOA: BENZOS BIND ON THE BENZO SITE BETWEEN ALPHA-1 AND GAMMA SUBUNITS ON GABAa RECEPTORS, (BETA SUBUNIT IS ALSO REQUIRED FOR ACTION) THEN USING ALLOSTERIC MODULATION TO ENHANCE GABA BINDING ON THE GABA SITE OF THE GABAa RECEPTOR, AND THEREFORE 'FREQUENCY' OF CL- CHANNEL OPENING, WHICH CAUSES CNS INHIBITORY EFFECTS AND THE DESIRED ANTI-ANXIETY AND MINOR MUSCLE RELAXING EFFECTS.
• -INHIBIT ADENOSINE UPTAKE ALONG WITH PRETTY MUCH EVERY CA+ STIMULATORY TYPE MECHANISM

70-90% PROTEIN BOUND, WITH UNBOUND % BEING DIRECTLY CORRELATED WITH CSF CONCENTRATION (MEANING UNBOUND BENZOS UNDOUBTEDLY CROSS THE BBB)

AMBIEN

• -1/2 LIFE 2 HRS
• -INFREQUENT TOLERANCE OR - DEPENDANCE
• -FOOD SLOWS ABSORPTION AND ONSET OF SLEEP
• -DIBASIC FORM AVAILABLE

MELATONIN RECEPTOR AGONIST

DECREASES SLEEP LATENCY

METABOLIZED BY CYP1A2, AS IS FLUVOXAMINE (SSRI), SO SHOULD NOT BE TAKEN SIMULTANEOUSLY WITH FLUVOXAMINE, AS TOXIC BUILDUP COULD OCCUR

NO REBOUND INSOMNIA, NO WITHDRAWAL SYMPTOMS

SELECTIVE FOR MT1 AND MT2 MELATONIN RECEPTORS, AND IS ACTUALLY 6 TIMES MORE SELECTIVE FOR MT1 THAN ENDOGENOUS MELATONIN

JFYI: AGONIZING MT1 INDUCES SLEEPINESS, AGONIZING MT2 PREFERENTIALLY INFLUENCES REGULATION OF CIRCADIAN SLEEP RHYTHMS.

ROZEREM

BARBITURATE, ANTICONVULSANT

• MOA:
• -BARBITURATES BIND AND AGONIZE THE BARBITURATE BINDING SITE ON ALPHA SUBUNITS OF GABAa RECEPTORS. BETA SUBUNITS ARE ALSO REQUIRED FOR ACTIVITY.
• -THIS INCREASES GABA BINDING TO THE GABAa RECEPTOR, WHICH INCREASES INHIBITORY TRANSMISSION AND 'DURATION' OF CL- CHANNEL OPENING. INCREASING DURATION OF CL- CHANNEL OPENING LEADS TO INCREASED 'EFFICACY' OF GABA INHIBITORY EFFECTS.
• -GLUTAMATE AMPA RECEPTOR BLOCKER.
• THIS HELPS INHIBIT EXCITATORY TRANSMISSION
• -LOWER (NOT BLOCK, BUT JUST LOWER) GANGLIONIC, NICOTINIC, AND NEUROMUSCULAR ACTIVITY BY THE ABOVE MECHANISMS

LUMINAL

NOTE: BARBS INCREASE 'DURATION' OF CL- CHANNEL OPENING, AND THEREFORE 'EFFICACY' OF ACTION. IN CONTRAST, BENZOS INCREASE 'FREQUENCY' OF CL- CHANNEL OPENING, AND THEREFORE 'POTENCY' OF ACTION. THIS DIRECT AND LONGER TERM GATING IS THE KEY DIFFERENCE IN TOXICITY AND POTENTIAL HARM OF BARBS, AND WHY BENZOS ARE PREFERRED OVER BARBS FOR MOST CASES TODAY.

RESULTS IN DOWN REGULATION OF GABAa RECEPTORS IN AN ATTEMPT TO COUNTERACT THE SUDDEN DECREASE OVERALL DECREASE IN STIMULATION

BARBITURATE

• MOA: -BARBITURATES BIND AND AGONIZE THE BARBITURATE BINDING SITE ON ALPHA SUBUNITS OF GABAa RECEPTORS. BETA SUBUNITS ARE ALSO REQUIRED FOR ACTIVITY.-THIS INCREASES GABA BINDING TO THE GABAa RECEPTOR, WHICH INCREASES INHIBITORY TRANSMISSION AND 'DURATION' OF CL- CHANNEL OPENING. INCREASING DURATION OF CL- CHANNEL OPENING LEADS TO INCREASED 'EFFICACY' OF GABA INHIBITORY EFFECTS.-GLUTAMATE AMPA RECEPTOR BLOCKER. THIS HELPS INHIBIT EXCITATORY TRANSMISSION
• -LOWER (NOT BLOCK, BUT JUST LOWER) GANGLIONIC, NICOTINIC, AND NEUROMUSCULAR ACTIVITY BY THE ABOVE MECHANISMS

BUTISOL

NOTE: BARBS INCREASE 'DURATION' OF CL- CHANNEL OPENING, AND THEREFORE 'EFFICACY' OF ACTION. IN CONTRAST, BENZOS INCREASE 'FREQUENCY' OF CL- CHANNEL OPENING, AND THEREFORE 'POTENCY' OF ACTION. THIS DIRECT AND LONGER TERM GATING IS THE KEY DIFFERENCE IN TOXICITY AND POTENTIAL HARM OF BARBS, AND WHY BENZOS ARE PREFERRED OVER BARBS FOR MOST CASES TODAY.

BARBITURATE

• MOA: -BARBITURATES BIND AND AGONIZE THE BARBITURATE BINDING SITE ON ALPHA SUBUNITS OF GABAa RECEPTORS. BETA SUBUNITS ARE ALSO REQUIRED FOR ACTIVITY.-THIS INCREASES GABA BINDING TO THE GABAa RECEPTOR, WHICH INCREASES INHIBITORY TRANSMISSION AND 'DURATION' OF CL- CHANNEL OPENING. INCREASING DURATION OF CL- CHANNEL OPENING LEADS TO INCREASED 'EFFICACY' OF GABA INHIBITORY EFFECTS.-GLUTAMATE AMPA RECEPTOR BLOCKER. THIS HELPS INHIBIT EXCITATORY TRANSMISSION
• -LOWER (NOT BLOCK, BUT JUST LOWER) GANGLIONIC, NICOTINIC, AND NEUROMUSCULAR ACTIVITY BY THE ABOVE MECHANISMS

NEMBUTAL

NOTE: BARBS INCREASE 'DURATION' OF CL- CHANNEL OPENING, AND THEREFORE 'EFFICACY' OF ACTION. IN CONTRAST, BENZOS INCREASE 'FREQUENCY' OF CL- CHANNEL OPENING, AND THEREFORE 'POTENCY' OF ACTION. THIS DIRECT AND LONGER TERM GATING IS THE KEY DIFFERENCE IN TOXICITY AND POTENTIAL HARM OF BARBS, AND WHY BENZOS ARE PREFERRED OVER BARBS FOR MOST CASES TODAY.

BARBITURATE

• MOA: -BARBITURATES BIND AND AGONIZE THE BARBITURATE BINDING SITE ON ALPHA SUBUNITS OF GABAa RECEPTORS. BETA SUBUNITS ARE ALSO REQUIRED FOR ACTIVITY.-THIS INCREASES GABA BINDING TO THE GABAa RECEPTOR, WHICH INCREASES INHIBITORY TRANSMISSION AND 'DURATION' OF CL- CHANNEL OPENING. INCREASING DURATION OF CL- CHANNEL OPENING LEADS TO INCREASED 'EFFICACY' OF GABA INHIBITORY EFFECTS.-GLUTAMATE AMPA RECEPTOR BLOCKER. THIS HELPS INHIBIT EXCITATORY TRANSMISSION
• -LOWER (NOT BLOCK, BUT JUST LOWER) GANGLIONIC, NICOTINIC, AND NEUROMUSCULAR ACTIVITY BY THE ABOVE MECHANISMS

SECONAL, TUINAL

NOTE: BARBS INCREASE 'DURATION' OF CL- CHANNEL OPENING, AND THEREFORE 'EFFICACY' OF ACTION. IN CONTRAST, BENZOS INCREASE 'FREQUENCY' OF CL- CHANNEL OPENING, AND THEREFORE 'POTENCY' OF ACTION. THIS DIRECT AND LONGER TERM GATING IS THE KEY DIFFERENCE IN TOXICITY AND POTENTIAL HARM OF BARBS, AND WHY BENZOS ARE PREFERRED OVER BARBS FOR MOST CASES TODAY.

BARBITURATE

• MOA: -BARBITURATES BIND AND AGONIZE THE BARBITURATE BINDING SITE ON ALPHA SUBUNITS OF GABAa RECEPTORS. BETA SUBUNITS ARE ALSO REQUIRED FOR ACTIVITY.-THIS INCREASES GABA BINDING TO THE GABAa RECEPTOR, WHICH INCREASES INHIBITORY TRANSMISSION AND 'DURATION' OF CL- CHANNEL OPENING. INCREASING DURATION OF CL- CHANNEL OPENING LEADS TO INCREASED 'EFFICACY' OF GABA INHIBITORY EFFECTS.-GLUTAMATE AMPA RECEPTOR BLOCKER. THIS HELPS INHIBIT EXCITATORY TRANSMISSION
• -LOWER (NOT BLOCK, BUT JUST LOWER) GANGLIONIC, NICOTINIC, AND NEUROMUSCULAR ACTIVITY BY THE ABOVE MECHANISMS

PENTOTHAL

NOTE: BARBS INCREASE 'DURATION' OF CL- CHANNEL OPENING, AND THEREFORE 'EFFICACY' OF ACTION. IN CONTRAST, BENZOS INCREASE 'FREQUENCY' OF CL- CHANNEL OPENING, AND THEREFORE 'POTENCY' OF ACTION. THIS DIRECT AND LONGER TERM GATING IS THE KEY DIFFERENCE IN TOXICITY AND POTENTIAL HARM OF BARBS, AND WHY BENZOS ARE PREFERRED OVER BARBS FOR MOST CASES TODAY.

BARBITURATE

• MOA: -BARBITURATES BIND AND AGONIZE THE BARBITURATE BINDING SITE ON ALPHA SUBUNITS OF GABAa RECEPTORS. BETA SUBUNITS ARE ALSO REQUIRED FOR ACTIVITY.-THIS INCREASES GABA BINDING TO THE GABAa RECEPTOR, WHICH INCREASES INHIBITORY TRANSMISSION AND 'DURATION' OF CL- CHANNEL OPENING. INCREASING DURATION OF CL- CHANNEL OPENING LEADS TO INCREASED 'EFFICACY' OF GABA INHIBITORY EFFECTS.-GLUTAMATE AMPA RECEPTOR BLOCKER. THIS HELPS INHIBIT EXCITATORY TRANSMISSION
• -LOWER (NOT BLOCK, BUT JUST LOWER) GANGLIONIC, NICOTINIC, AND NEUROMUSCULAR ACTIVITY BY THE ABOVE MECHANISMS

BREVITAL

NOTE: BARBS INCREASE 'DURATION' OF CL- CHANNEL OPENING, AND THEREFORE 'EFFICACY' OF ACTION. IN CONTRAST, BENZOS INCREASE 'FREQUENCY' OF CL- CHANNEL OPENING, AND THEREFORE 'POTENCY' OF ACTION. THIS DIRECT AND LONGER TERM GATING IS THE KEY DIFFERENCE IN TOXICITY AND POTENTIAL HARM OF BARBS, AND WHY BENZOS ARE PREFERRED OVER BARBS FOR MOST CASES TODAY.

GENERALIZED ANXIETY DISORDER

MOA: LARGELY UNKNOWN, BUT IS A STRONG AGONIST AT PRE-SYNAPTIC 5HT-1A RECEPTORS IN RAPHE NUCLEI, AND SOME AGONISTIC EFFECT ON POST-SYNAPTIC 5HT-1A RECEPTORS IN HIPPOCAMPUS AND CORTEX. THIS EVENTUALLY CAUSES DOWN REGULATION OF THESE 5HT-1 RECEPTORS, WHICH CAN HAVE ANXIETY AND DEPRESSION LOWERING PROPERTIES. HAS NO EFFECT ON BZD-GABAa RECEPTORS

SHOWN TO HAVE LESS POTENTIAL FOR ABUSE THAN BENZOS. CAUSES FAR LESS SOMNOLENCE THAN BENZOS AS WELL.

BUSPAR

NON-BENZO HYPNOTIC

MOA: MOSTLY UNKNOWN, BUT IT IS METABOLIZED BY OH DEHYDROGENASE INTO THE METABOLITE TRICHLOROETHANOL, WHICH CAUSES ITS CNS DEPRESSANT EFFECTS

NOCTEC, SOMNOTE

CAUSES ADVERSE GI EFFECTS ON AN EMPTY STOMACH (JUST LIKE ALCOHOLIC DRINKS)

ANTICONVULSANT, MUSCLE RELAXANT

NOT A BARB OR BENZO

PLACIDYL

• NOT AVAILABLE IN US SINCE 1999
• EXTREMELY POWERFUL AND ADDICTIVE

• JFYI/RANDOM FACT
• Former Chief Justice of the Supreme Court of the United States of America William Rehnquist was addicted to ethchlorvynol from 1970 to 1981, and required an inpatient detoxification to discontinue the drug.

NON BENZO ANTI-ANXIETY AGENT (NIGHT-TIME SEDATIVE), ALTHOUGH ACTIONS ARE SIMILAR TO BENZOS

MOA: AFFECTS THALAMUS AND LIMBIC SYSTEM, ALSO INHIBITS MULTINEURONAL SPINAL REFLEXES (LEXICOMP)

MILTOWN

TERTIARY AMINE TRICYCLIC ANTIDEPRESSANT

MOA: SNRI (MAINLY SERT) + OTHERS

• -AIM IS TO GET MORE SEROTONIN TRANSMISSION FROM THE PRE-SYNAPTIC CELLS IN THE RAPHE NUCLEI TO THE POST-SYNAPTIC CELLS OF THE FRONTAL CORTEX
• -SNRI ACTIVITY(MORE SO BLOCKS SERT)
• -CAUSE DOWN REGULATION BY BEING AN AGONIST AT 5HT1-A&D(Gi COUPLED) RECEPTORS.(THIS MIGHT INITIALLY CAUSE A DEEPER DEPRESSION UNTIL DOWN REGULATION OCCURS!) THESE RECEPTORS NORMALLY INHIBIT SEROTONIN RELEASE, SO WHEN THEY ARE EVENTUALLY DOWN REGULATED, MORE SEROTONIN IS ABLE TO BE RELEASED FROM THE PRE-SYNAPTIC RAPHE NUCLEI CELLS TO BE ABLE TO REACH THE POST-SYNAPTIC FRONTAL CORTEX CELLS. AMITRIPTYLINE ALSO BLOCKS POST-SYNAPTIC 5HT-2 (Gq COUPLED) CELLS OF THE FRONTAL CORTEX, AND EVENTUALLY LEADS TO THEIR DOWN REGULATION. THESE POST-SYNAPTIC 5HT-2 RECEPTORS NORMALLY LOWER 5HT TRANSMISSION (SO DON'T BE FOOLED BY THE FACT THAT THEY ARE Gq COUPLED!) SO THEIR BLOCKAGE AND/OR DOWN REGULATION INCREASES 5HT TRANSMISSION. THIS DOWN REGULATION OF BOTH PRE AND POST-SYNAPTIC CELLS IS LIKELY THE REASON FOR DELAYED THERAPEUTIC EFFECTS IN TRICYCLIC ANTIDEPRESSANTS, AS IT TAKES WEEKS.
• -THESE COMBINED MECHANISMS OF ACTION THEORETICALLY INCREASE cAMP IN THE POST-SYNAPTIC FRONTAL CORTEX CELLS, WHICH ACTIVATES CREB PROTEINS, WHICH THEN BIND TO DNA AND INCREASE TRANSLATION OF BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) PROTEINS, WHICH ARE IMPORTANT IN NEURONAL CELL HEALTH AND HOMEOSTASIS.

THE LOWER THE Ki VALUE(INHIBITION CONSTANT) THE MORE POTENT AN INHIBITOR

IS A SERT SELECTIVE BLOCKING TERTIARY AMINE TCA, BUT IS METABOLIZED BY N-DEMETHYLATION INTO A SECONDARY AMINE TCA CALLED NORTRIPTYLINE, WHICH IS OF COURSE MORE NET SELECTIVE, MORE STIMULATORY, LESS ANTICHOLINERGIC, AND LESS ANTI-HISTAMINIC AS SECONDARY AMINE TCAs TEND TO BE.

ALL TCAs (ESPECIALLY TERTIARY AMINES) HAVE SOME DEGREE OF MUSCARINIC, ALPHA-1, H-1, AND NA+ CHANNEL BLOCKING (SIDE EFFECTS!)

NOTE: TERTIARY AMINE TRICYCLIC ANTIDEPRESSANTS INHIBIT SERT MORE THAN NET!

ELAVIL

TERTIARY AMINE TRICYCLIC ANTIDEPRESSANT (5HT AND NE)

MOA: SNRI (MAINLY SERT) + OTHERS

• -AIM IS TO GET MORE SEROTONIN TRANSMISSION FROM THE PRE-SYNAPTIC CELLS IN THE RAPHE NUCLEI TO THE POST-SYNAPTIC CELLS OF THE FRONTAL CORTEX
• -SNRI ACTIVITY(MORE SO BLOCKS SERT)
• -CAUSE DOWN REGULATION BY BEING AN AGONIST AT 5HT1-A&D(Gi COUPLED) RECEPTORS.(THIS INITIALLY WORSENS DEPRESSION UNTIL DOWNREGULATION OCCURS!) THESE RECEPTORS NORMALLY INHIBIT SEROTONIN RELEASE, SO WHEN THEY ARE DOWN REGULATED, MORE SEROTONIN IS ABLE TO BE RELEASED FROM THE PRE-SYNAPTIC RAPHE NUCLEI CELLS TO BE ABLE TO REACH THE POST-SYNAPTIC FRONTAL CORTEX CELLS. AMITRIPTYLINE ALSO BLOCKS POST-SYNAPTIC 5HT-2 (Gq COUPLED) CELLS OF THE FRONTAL CORTEX, AND EVENTUALLY LEADS TO THEIR DOWN REGULATION. THESE POST-SYNAPTIC 5HT-2 RECEPTORS NORMALLY LOWER 5HT TRANSMISSION (SO DON'T BE FOOLED BY THE FACT THAT THEY ARE Gq COUPLED!) SO THEIR BLOCKAGE AND/OR DOWN REGULATION INCREASES 5HT TRANSMISSION. THIS DOWN REGULATION OF BOTH PRE AND POST-SYNAPTIC CELLS IS LIKELY THE REASON FOR DELAYED THERAPEUTIC EFFECTS IN TRICYCLIC ANTIDEPRESSANTS, AS IT TAKES WEEKS.

-THESE COMBINED MECHANISMS OF ACTION THEORETICALLY INCREASE cAMP IN THE POST-SYNAPTIC FRONTAL CORTEX CELLS, WHICH ACTIVATES CREB PROTEINS, WHICH THEN BIND TO DNA AND INCREASE TRANSLATION OF BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) PROTEINS, WHICH ARE IMPORTANT IN NEURONAL CELL HEALTH AND HOMEOSTASIS.

THE LOWER THE Ki VALUE(INHIBITION CONSTANT) THE MORE POTENT AN INHIBITOR

IT'S SECONDARY METABOLITE IS THE SECONDARY AMINE TCA KNOWN AS DESIPRAMINE. DESIPRAMINE ACTUALLY CONTRIBUTES MOST OF THE ANTIDEPRESSANT ACTIVITY, IS LESS ANTICHOLINERGIC, LESS SEDATIVE, MORE NET SELECTIVE, AND MORE STIMULATORY, AS ARE ALL SECONDARY AMINE TCAs WHEN COMPARED TO TERTIARY TCAs.

ALL TCAs (ESPECIALLY TERTIARY AMINES) HAVE SOME DEGREE OF MUSCARINIC, ALPHA-1, H-1, AND NA+ CHANNEL BLOCKING (SIDE EFFECTS!)

NOTE: TERTIARY AMINE TRICYCLIC ANTIDEPRESSANTS INHIBIT SERT MORE THAN NET!

TOFRANIL

TERTIARY AMINE TRICYCLIC ANTIDEPRESSANT (5HT AND NE)

• MOA: SNRI (MAINLY SERT) + OTHERS
• -AIM IS TO GET MORE SEROTONIN TRANSMISSION FROM THE PRE-SYNAPTIC CELLS IN THE RAPHE NUCLEI TO THE POST-SYNAPTIC CELLS OF THE FRONTAL CORTEX
• -SNRI ACTIVITY(MORE SO BLOCKS SERT)
• -CAUSE DOWN REGULATION BY BEING AN AGONIST AT 5HT1-A&D(Gi COUPLED) RECEPTORS.(THIS INITIALLY WORSENS THE DEPRESSION UNTIL DOWN REGULATION OCCURS!) THESE RECEPTORS NORMALLY INHIBIT SEROTONIN RELEASE, SO WHEN THEY ARE DOWN REGULATED, MORE SEROTONIN IS ABLE TO BE RELEASED FROM THE PRE-SYNAPTIC RAPHE NUCLEI CELLS TO BE ABLE TO REACH THE POST-SYNAPTIC FRONTAL CORTEX CELLS. AMITRIPTYLINE ALSO BLOCKS POST-SYNAPTIC 5HT-2 (Gq COUPLED) CELLS OF THE FRONTAL CORTEX, AND EVENTUALLY LEADS TO THEIR DOWN REGULATION. THESE POST-SYNAPTIC 5HT-2 RECEPTORS NORMALLY LOWER 5HT TRANSMISSION (SO DON'T BE FOOLED BY THE FACT THAT THEY ARE Gq COUPLED!) SO THEIR BLOCKAGE AND/OR DOWN REGULATION INCREASES 5HT TRANSMISSION. THIS DOWN REGULATION OF BOTH PRE AND POST-SYNAPTIC CELLS IS LIKELY THE REASON FOR DELAYED THERAPEUTIC EFFECTS IN TRICYCLIC ANTIDEPRESSANTS, AS IT TAKES WEEKS.

-THESE COMBINED MECHANISMS OF ACTION THEORETICALLY INCREASE cAMP IN THE POST-SYNAPTIC FRONTAL CORTEX CELLS, WHICH ACTIVATES CREB PROTEINS, WHICH THEN BIND TO DNA AND INCREASE TRANSLATION OF BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) PROTEINS, WHICH ARE IMPORTANT IN NEURONAL CELL HEALTH AND HOMEOSTASIS.

THE LOWER THE Ki VALUE(INHIBITION CONSTANT), THE MORE POTENT AN INHIBITOR

HAS A UNIQUE OXYGEN AT TOP OF MIDDLE RING. Z ISOMER IS MORE ACTIVE.

ALL TCAs (ESPECIALLY TERTIARY AMINES) HAVE SOME DEGREE OF MUSCARINIC, ALPHA-1, H-1, AND NA+ CHANNEL BLOCKING (SIDE EFFECTS!)

NOTE: TERTIARY AMINE TRICYCLIC ANTIDEPRESSANTS INHIBIT SERT MORE THAN NET!

ADAPIN, SINEQUAN

TERTIARY AMINE TRICYCLIC ANTIDEPRESSANT (5HT AND NE)

• MOA: SNRI (MAINLY SERT) + OTHERS
• -AIM IS TO GET MORE SEROTONIN TRANSMISSION FROM THE PRE-SYNAPTIC CELLS IN THE RAPHE NUCLEI TO THE POST-SYNAPTIC CELLS OF THE FRONTAL CORTEX
• -SNRI ACTIVITY(MORE SO BLOCKS SERT)
• -CAUSE DOWN REGULATION BY BEING AN AGONIST AT 5HT1-A&D(Gi COUPLED) RECEPTORS.(THIS INITIALLY WORSENS THE DEPRESSION IN SOME CASES UNTIL THE DOWN REGULATION HAPPENS!) THESE RECEPTORS NORMALLY INHIBIT SEROTONIN RELEASE, SO WHEN THEY ARE DOWN REGULATED, MORE SEROTONIN IS ABLE TO BE RELEASED FROM THE PRE-SYNAPTIC RAPHE NUCLEI CELLS TO BE ABLE TO REACH THE POST-SYNAPTIC FRONTAL CORTEX CELLS. AMITRIPTYLINE ALSO BLOCKS POST-SYNAPTIC 5HT-2 (Gq COUPLED) CELLS OF THE FRONTAL CORTEX, AND EVENTUALLY LEADS TO THEIR DOWN REGULATION. THESE POST-SYNAPTIC 5HT-2 RECEPTORS NORMALLY LOWER 5HT TRANSMISSION (SO DON'T BE FOOLED BY THE FACT THAT THEY ARE Gq COUPLED!) SO THEIR BLOCKAGE AND/OR DOWN REGULATION INCREASES 5HT TRANSMISSION. THIS DOWN REGULATION OF BOTH PRE AND POST-SYNAPTIC CELLS IS LIKELY THE REASON FOR DELAYED THERAPEUTIC EFFECTS IN TRICYCLIC ANTIDEPRESSANTS, AS IT TAKES WEEKS.

-THESE COMBINED MECHANISMS OF ACTION THEORETICALLY INCREASE cAMP IN THE POST-SYNAPTIC FRONTAL CORTEX CELLS, WHICH ACTIVATES CREB PROTEINS, WHICH THEN BIND TO DNA AND INCREASE TRANSLATION OF BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) PROTEINS, WHICH ARE IMPORTANT IN NEURONAL CELL HEALTH AND HOMEOSTASIS.

THE LOWER THE Ki VALUE(INHIBITION CONSTANT) THE MORE POTENT AN INHIBITOR

A 3-CHLORIDE DERIVATIVE OF IMIPRAMINE. THE CHLORIDE MAKES IT 50X MORE POTENT, AND MORE LIPOPHILIC AND BBB-X. CL ALSO MAKES IT MORE SERT SELECTIVE. WAS FIRST OCD TREATMENT OPTION.

ALL TCAs (ESPECIALLY TERTIARY AMINES) HAVE SOME DEGREE OF MUSCARINIC, ALPHA-1, H-1, AND NA+ CHANNEL BLOCKING (SIDE EFFECTS!)

NOTE: TERTIARY AMINE TRICYCLIC ANTIDEPRESSANTS INHIBIT SERT MORE THAN NET!

ANAFRANIL

TERTIARY AMINE TRICYCLIC ANTIDEPRESSANT (5HT AND NE)

• MOA: SNRI (MAINLY SERT) + OTHERS
• -AIM IS TO GET MORE SEROTONIN TRANSMISSION FROM THE PRE-SYNAPTIC CELLS IN THE RAPHE NUCLEI TO THE POST-SYNAPTIC CELLS OF THE FRONTAL CORTEX
• -SNRI ACTIVITY(MORE BLOCKS SERT)
• -CAUSE DOWN REGULATION BY BEING AN AGONIST AT 5HT1-A&D(Gi COUPLED) RECEPTORS.(THIS COULD INITIALLY WORSEN THE DEPRESSION SYMPTOMS UNTIL DOWN REGULATION OCCURS!) THESE RECEPTORS NORMALLY INHIBIT SEROTONIN RELEASE, SO WHEN THEY ARE DOWN REGULATED, MORE SEROTONIN IS ABLE TO BE RELEASED FROM THE PRE-SYNAPTIC RAPHE NUCLEI CELLS TO BE ABLE TO REACH THE POST-SYNAPTIC FRONTAL CORTEX CELLS. AMITRIPTYLINE ALSO BLOCKS POST-SYNAPTIC 5HT-2 (Gq COUPLED) CELLS OF THE FRONTAL CORTEX, AND EVENTUALLY LEADS TO THEIR DOWN REGULATION. THESE POST-SYNAPTIC 5HT-2 RECEPTORS NORMALLY LOWER 5HT TRANSMISSION (SO DON'T BE FOOLED BY THE FACT THAT THEY ARE Gq COUPLED!) SO THEIR BLOCKAGE AND/OR DOWN REGULATION INCREASES 5HT TRANSMISSION. THIS DOWN REGULATION OF BOTH PRE AND POST-SYNAPTIC CELLS IS LIKELY THE REASON FOR DELAYED THERAPEUTIC EFFECTS IN TRICYCLIC ANTIDEPRESSANTS, AS IT TAKES WEEKS.
• -THESE COMBINED MECHANISMS OF ACTION THEORETICALLY INCREASE cAMP IN THE POST-SYNAPTIC FRONTAL CORTEX CELLS, WHICH ACTIVATES CREB PROTEINS, WHICH THEN BIND TO DNA AND INCREASE TRANSLATION OF BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) PROTEINS, WHICH ARE IMPORTANT IN NEURONAL CELL HEALTH AND HOMEOSTASIS.

THE LOWER THE Ki VALUE(INHIBITION CONSTANT) THE MORE POTENT AN INHIBITOR

ALL TCAs (ESPECIALLY TERTIARY AMINES) HAVE SOME DEGREE OF MUSCARINIC, ALPHA-1, H-1, AND NA+ CHANNEL BLOCKING (SIDE EFFECTS!)

NOTE: TERTIARY AMINE TRICYCLIC ANTIDEPRESSANTS INHIBIT SERT MORE THAN NET!

SURMONTIL

TETRACYCLIC ANTIDEPRESSANT(NE&DA)

AND/OR (DEPENDING ON THE AUTHORITY THAT CLASSIFIES IT)--

SECONDARY AMINE TRICYCLIC ANTIDEPRESSANT (NE AND DA)

MOA:

-GOES THROUGH SIMILAR DESENSITIZATION PROCESS TO TERTIARY AMINE TCAs, EXCEPT THE RECEPTORS BEING DESENSITIZED ARE PRE-SYNAPTIC ALPHA-2 (WHICH WOULD NORMALLY INHIBIT NE TRANSMISSION FROM THE PRE-SYNAPTIC LOCUS COERULEUS TO THE POST-SYNAPTIC FRONTAL CORTEX NEURONS). POST-SYNAPTIC ALPHA-1 AND VARIOUS BETA RECEPTORS (INDIRECTLY LEADING TO ENHANCED 5HT FUNCTION) ON THE FRONTAL CORTEX ALSO BECOME DESENSITIZED, WHICH MAY OR MAY NOT CONTRIBUTE TO ANTIDEPRESSANT EFFECTS, ALTHOUGH LIKELY TO SIDE EFFECTS AS WELL. THE MOST IMPORTANT MOA IS LIKELY THE SELECTIVE INHIBITION OF REUPTAKE BY NET, WHICH LEAVES MORE NE TO ACT ON POST-SYNAPTIC ADRENERGIC RECEPTORS IN THE POST-SYNAPTIC FRONTAL CORTEX REGION.

-THIS SOMEHOW LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SECONDARY AMINE TCAs ARE GENERALLY LESS ANTICHOLINERGIC, LESS SEDATIVE, MORE STIMULATORY, AND MORE SELECTIVE FOR NET INHIBITION OVER SERT.

ASCENDIN

AGAIN, NOTE THAT THIS DRUG IS UNIQUE IN ITS ABILITY TO INHIBIT REUPTAKE OF NOT ONLY NE, BUT ALSO DA!

SECONDARY AMINE TRICYCLIC ANTIDEPRESSANT (NE ONLY)

MOA:

-GOES THROUGH SIMILAR DESENSITIZATION PROCESS TO TERTIARY AMINE TCAs, EXCEPT THE RECEPTORS BEING DESENSITIZED ARE PRE-SYNAPTIC ALPHA-2 (WHICH WOULD NORMALLY INHIBIT NE TRANSMISSION FROM THE PRE-SYNAPTIC LOCUS COERULEUS TO THE POST-SYNAPTIC FRONTAL CORTEX NEURONS). POST-SYNAPTIC ALPHA-1 AND VARIOUS BETA RECEPTORS (INDIRECTLY LEADING TO ENHANCED 5HT FUNCTION) ON THE FRONTAL CORTEX ALSO BECOME DESENSITIZED, WHICH MAY OR MAY NOT CONTRIBUTE TO ANTIDEPRESSANT EFFECTS, ALTHOUGH LIKELY TO SIDE EFFECTS AS WELL. THE MOST IMPORTANT MOA IS LIKELY THE SELECTIVE INHIBITION OF REUPTAKE BY NET, WHICH LEAVES MORE NE TO ACT ON POST-SYNAPTIC ADRENERGIC RECEPTORS IN THE POST-SYNAPTIC FRONTAL CORTEX REGION.

-THIS SOMEHOW LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SECONDARY AMINE TCAs ARE GENERALLY LESS ANTICHOLINERGIC, LESS SEDATIVE, MORE STIMULATORY, AND MORE SELECTIVE FOR NET INHIBITION OVER SERT.

NORPRAMIN

SECONDARY AMINE TRICYCLIC ANTIDEPRESSANT (NE ONLY)

MOA:-GOES THROUGH SIMILAR DESENSITIZATION PROCESS TO TERTIARY AMINE TCAs, EXCEPT THE RECEPTORS BEING DESENSITIZED ARE PRE-SYNAPTIC ALPHA-2 (WHICH WOULD NORMALLY INHIBIT NE TRANSMISSION FROM THE PRE-SYNAPTIC LOCUS COERULEUS TO THE POST-SYNAPTIC FRONTAL CORTEX NEURONS). POST-SYNAPTIC ALPHA-1 AND VARIOUS BETA RECEPTORS (INDIRECTLY LEADING TO ENHANCED 5HT FUNCTION) ON THE FRONTAL CORTEX ALSO BECOME DESENSITIZED, WHICH MAY OR MAY NOT CONTRIBUTE TO ANTIDEPRESSANT EFFECTS, ALTHOUGH LIKELY TO SIDE EFFECTS AS WELL. THE MOST IMPORTANT MOA IS LIKELY THE SELECTIVE INHIBITION OF REUPTAKE BY NET, WHICH LEAVES MORE NE TO ACT ON POST-SYNAPTIC ADRENERGIC RECEPTORS IN THE POST-SYNAPTIC FRONTAL CORTEX REGION.

-THIS SOMEHOW LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SECONDARY AMINE TCAs ARE GENERALLY LESS ANTICHOLINERGIC, LESS SEDATIVE, MORE STIMULATORY, AND MORE SELECTIVE FOR NET INHIBITION OVER SERT.

NORTRIPTYLINE IS A SECONDARY METABOLITE (N-DEMETHYLATED) OF AMITRIPTYLINE (A TERTIARY AMINE TCA) WHICH IS ANOTHER PRODUCT SOLD SEPARATELY ON OUR DRUG LIST.

PAMELOR

SECONDARY AMINE TRICYCLIC ANTIDEPRESSANT (NE ONLY)

MOA:

-GOES THROUGH SIMILAR DESENSITIZATION PROCESS TO TERTIARY AMINE TCAs, EXCEPT THE RECEPTORS BEING DESENSITIZED ARE PRE-SYNAPTIC ALPHA-2 (WHICH WOULD NORMALLY INHIBIT NE TRANSMISSION FROM THE PRE-SYNAPTIC LOCUS COERULEUS TO THE POST-SYNAPTIC FRONTAL CORTEX NEURONS). POST-SYNAPTIC ALPHA-1 AND VARIOUS BETA RECEPTORS (INDIRECTLY LEADING TO ENHANCED 5HT FUNCTION) ON THE FRONTAL CORTEX ALSO BECOME DESENSITIZED, WHICH MAY OR MAY NOT CONTRIBUTE TO ANTIDEPRESSANT EFFECTS, ALTHOUGH LIKELY TO SIDE EFFECTS AS WELL. THE MOST IMPORTANT MOA IS LIKELY THE SELECTIVE INHIBITION OF REUPTAKE BY NET, WHICH LEAVES MORE NE TO ACT ON POST-SYNAPTIC ADRENERGIC RECEPTORS IN THE POST-SYNAPTIC FRONTAL CORTEX REGION.

-THIS SOMEHOW LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SECONDARY AMINE TCAs ARE GENERALLY LESS ANTICHOLINERGIC, LESS SEDATIVE, MORE STIMULATORY, AND MORE SELECTIVE FOR NET INHIBITION OVER SERT.

VIVACTIL

TETRACYCLIC ANTIDEPRESSANT(NE)

AND/OR (DEPENDING ON THE CLASSIFYING AUTHORITY)---

SECONDARY AMINE TRICYCLIC ANTIDEPRESSANT (NE ONLY)

MOA:

-GOES THROUGH SIMILAR DESENSITIZATION PROCESS TO TERTIARY AMINE TCAs, EXCEPT THE RECEPTORS BEING DESENSITIZED ARE PRE-SYNAPTIC ALPHA-2 (WHICH WOULD NORMALLY INHIBIT NE TRANSMISSION FROM THE PRE-SYNAPTIC LOCUS COERULEUS TO THE POST-SYNAPTIC FRONTAL CORTEX NEURONS). POST-SYNAPTIC ALPHA-1 AND VARIOUS BETA RECEPTORS (INDIRECTLY LEADING TO ENHANCED 5HT FUNCTION) ON THE FRONTAL CORTEX ALSO BECOME DESENSITIZED, WHICH MAY OR MAY NOT CONTRIBUTE TO ANTIDEPRESSANT EFFECTS, ALTHOUGH LIKELY TO SIDE EFFECTS AS WELL. THE MOST IMPORTANT MOA IS LIKELY THE SELECTIVE INHIBITION OF REUPTAKE BY NET, WHICH LEAVES MORE NE TO ACT ON POST-SYNAPTIC ADRENERGIC RECEPTORS IN THE POST-SYNAPTIC FRONTAL CORTEX REGION.

-THIS SOMEHOW LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SECONDARY AMINE TCAs ARE GENERALLY LESS ANTICHOLINERGIC, LESS SEDATIVE, MORE STIMULATORY, AND MORE SELECTIVE FOR NET INHIBITION OVER SERT.

LUDIOMIL

SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI)

MOA:

-MAINLY SSRI ACTIVITY IN RAPHE NUCLEI PRE-SYNAPTIC NEURONS, BUT ALSO EVENTUAL DESENSITIZATION AND/OR DOWNREGULATION OF PRE-SYNAPTIC 5HT-1A&D RECEPTORS, AND POST-SYNAPTIC 5HT-2 RECEPTORS WHICH ALL LEAD TO INCREASED 5HT NEUROTRANSMISSION AND THEREFORE OUR DESIRED ANTIDEPRESSANT EFFECTS.

-THIS ALL ALSO LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SSRIs ARE PREFERRED OVER TCAs DUE TO BEING MORE SPECIFIC, WHICH LEADS TO LESS SIDE EFFECTS. ALTHOUGH RECENT STUDIES HAVE SHOWN THAT EVEN SSRIs ONLY HAVE VERY NOTICEABLE ANTI-DEPRESSANT EFFECTS IN THOSE THAT ARE SEVERELY DEPRESSED.

SIDE EFFECTS: STIMULATION OF 5HT1 AND 5HT2 CAN LEAD TO DECREASED ORGANSM IN MALES AND FEMALES. STIMULATION OF 5HT-3 CAN LEAD TO NAUSEA AND VOMITING.

CELEXA

SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI)

MOA:

-MAINLY SSRI ACTIVITY IN RAPHE NUCLEI PRE-SYNAPTIC NEURONS, BUT ALSO EVENTUAL DESENSITIZATION AND/OR DOWNREGULATION OF PRE-SYNAPTIC 5HT-1A&D RECEPTORS, AND POST-SYNAPTIC 5HT-2 RECEPTORS WHICH ALL LEAD TO INCREASED 5HT NEUROTRANSMISSION AND THEREFORE OUR DESIRED ANTIDEPRESSANT EFFECTS.

-THIS ALL ALSO LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SSRIs ARE PREFERRED OVER TCAs DUE TO BEING MORE SPECIFIC, WHICH LEADS TO LESS SIDE EFFECTS. ALTHOUGH RECENT STUDIES HAVE SHOWN THAT EVEN SSRIs ONLY HAVE VERY NOTICEABLE ANTI-DEPRESSANT EFFECTS IN THOSE THAT ARE SEVERELY DEPRESSED.

SIDE EFFECTS: STIMULATION OF THE 5HT1 AND 5HT2 RECEPTORS CAN LEAD TO DECREASED SEXUAL FUNCTION IN MALES AND FEMALES. STIMULATION AT 5HT3 COULD LEAD TO NAUSEA AND VOMITING.

LEXAPRO

SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI)

MOA:

-MAINLY SSRI ACTIVITY IN RAPHE NUCLEI PRE-SYNAPTIC NEURONS, BUT ALSO EVENTUAL DESENSITIZATION AND/OR DOWNREGULATION OF PRE-SYNAPTIC 5HT-1A&D RECEPTORS, AND POST-SYNAPTIC 5HT-2 RECEPTORS WHICH ALL LEAD TO INCREASED 5HT NEUROTRANSMISSION AND THEREFORE OUR DESIRED ANTIDEPRESSANT EFFECTS.

-THIS ALL ALSO LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SSRIs ARE PREFERRED OVER TCAs DUE TO BEING MORE SPECIFIC, WHICH LEADS TO LESS SIDE EFFECTS. ALTHOUGH RECENT STUDIES HAVE SHOWN THAT EVEN SSRIs ONLY HAVE VERY NOTICEABLE ANTI-DEPRESSANT EFFECTS IN THOSE THAT ARE SEVERELY DEPRESSED.

SIDE EFFECTS: STIMULATION OF THE 5HT1 AND 5HT2 RECEPTORS CAN LEAD TO DECREASED SEXUAL FUNCTION IN MALES AND FEMALES. STIMULATION AT 5HT3 COULD LEAD TO NAUSEA AND VOMITING.

PROZAC

SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI)

MOA:

-MAINLY SSRI ACTIVITY IN RAPHE NUCLEI PRE-SYNAPTIC NEURONS, BUT ALSO EVENTUAL DESENSITIZATION AND/OR DOWNREGULATION OF PRE-SYNAPTIC 5HT-1A&D RECEPTORS, AND POST-SYNAPTIC 5HT-2 RECEPTORS WHICH ALL LEAD TO INCREASED 5HT NEUROTRANSMISSION AND THEREFORE OUR DESIRED ANTIDEPRESSANT EFFECTS.

-THIS ALL ALSO LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SSRIs ARE PREFERRED OVER TCAs DUE TO BEING MORE SPECIFIC, WHICH LEADS TO LESS SIDE EFFECTS. ALTHOUGH RECENT STUDIES HAVE SHOWN THAT EVEN SSRIs ONLY HAVE VERY NOTICEABLE ANTI-DEPRESSANT EFFECTS IN THOSE THAT ARE SEVERELY DEPRESSED.

• FLUVOXAMINE IS A MAJOR INHIBITOR OF MOST ALL CYP450 ENZYMES!
• EX: FLUVOXAMINE IS HEAVILY METABOLIZED BY CYP1A2, AS IS RAMELTION (MELATON AGONIST), SO THIS SHOULD NOT BE TAKEN WITH RAMELTEON AS TOXIC BUILDUP COULD OCCUR.

SIDE EFFECTS: STIMULATION OF THE 5HT1 AND 5HT2 RECEPTORS CAN LEAD TO DECREASED SEXUAL FUNCTION IN MALES AND FEMALES. STIMULATION AT 5HT3 COULD LEAD TO NAUSEA AND VOMITING.

LUVOX

SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI)

MOA:

-MAINLY SSRI ACTIVITY IN RAPHE NUCLEI PRE-SYNAPTIC NEURONS, BUT ALSO EVENTUAL DESENSITIZATION AND/OR DOWNREGULATION OF PRE-SYNAPTIC 5HT-1A&D RECEPTORS, AND POST-SYNAPTIC 5HT-2 RECEPTORS WHICH ALL LEAD TO INCREASED 5HT NEUROTRANSMISSION AND THEREFORE OUR DESIRED ANTIDEPRESSANT EFFECTS.

-THIS ALL ALSO LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SSRIs ARE PREFERRED OVER TCAs DUE TO BEING MORE SPECIFIC, WHICH LEADS TO LESS SIDE EFFECTS. ALTHOUGH RECENT STUDIES HAVE SHOWN THAT EVEN SSRIs ONLY HAVE VERY NOTICEABLE ANTI-DEPRESSANT EFFECTS IN THOSE THAT ARE SEVERELY DEPRESSED.

SIDE EFFECTS: STIMULATION OF THE 5HT1 AND 5HT2 RECEPTORS CAN LEAD TO DECREASED SEXUAL FUNCTION IN MALES AND FEMALES. STIMULATION AT 5HT3 COULD LEAD TO NAUSEA AND VOMITING.

PAXIL

SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI)

MOA:

-MAINLY SSRI ACTIVITY IN RAPHE NUCLEI PRE-SYNAPTIC NEURONS, BUT ALSO EVENTUAL DESENSITIZATION AND/OR DOWNREGULATION OF PRE-SYNAPTIC 5HT-1A&D RECEPTORS, AND POST-SYNAPTIC 5HT-2 RECEPTORS WHICH ALL LEAD TO INCREASED 5HT NEUROTRANSMISSION AND THEREFORE OUR DESIRED ANTIDEPRESSANT EFFECTS.

-THIS ALL ALSO LEADS TO INCREASED cAMP LEVELS, WHICH LEADS TO ACTIVATION OF CREB PROTEINS, WHICH LEADS TO INCREASED BDNF (BRAIN DERIVED NEUROTROPHIC FACTOR) EXPRESSION, WHICH IS NECESSARY FOR NEUROGENESIS AND HOMEOSTASIS.

SSRIs ARE PREFERRED OVER TCAs DUE TO BEING MORE SPECIFIC, WHICH LEADS TO LESS SIDE EFFECTS. ALTHOUGH RECENT STUDIES HAVE SHOWN THAT EVEN SSRIs ONLY HAVE VERY NOTICEABLE ANTI-DEPRESSANT EFFECTS IN THOSE THAT ARE SEVERELY DEPRESSED.

SIDE EFFECTS: STIMULATION OF THE 5HT1 AND 5HT2 RECEPTORS CAN LEAD TO DECREASED SEXUAL FUNCTION IN MALES AND FEMALES. STIMULATION AT 5HT3 COULD LEAD TO NAUSEA AND VOMITING.

ZOLOFT

SEROTONIN, NOREPINEPHRINE REUPTAKE INHIBITOR (SNRI)

VENLAFAXINE HAS VIRTUALLY IDENTICAL SERT AND NET INHIBITION, BUT IT'S SECONDARY METABOLITE DESVENLAFAXINE (PRISTIQ) IS 20X MORE POTENT FOR SERT INHIBITION, AND ACTUALLY CONTRIBUTES MOST OF THE ANTIDEPRESSANT EFFECT.

EFFEXOR

ITS METABOLITE IS DESVENLAFAXINE (PRISTIQ) WHICH IS AN EVEN MORE POTENT SNRI (THOUGH ALSO A MORE POTENT SERT INHIBITOR THAN NET INHIBITOR.

ALSO CONSIDERED "ATYPICAL ANTIDEPRESSANT"

SEROTONIN, NE REUPTAKE INHIBITOR (SNRI)

CYMBALTA

ALSO APPROVED FOR FIBROMYALGIA

ALSO IN "ATYPICAL ANTIDEPRESSANT GROUPING"

SEROTONIN, NE REUPTAKE INHIBITOR (SNRI)

20X MORE POTENT AT SERT INHIBITION THAN NET INHIBITION

PRISTIQ

• SECONDARY (AND MORE POTENT) METABOLITE OF VENLAFAXINE (EFFEXOR)
• DESVENLAFAXINE IS 20X MORE SELECTIVE FOR SERT THAN NET

ALSO CONSIDERED "ATYPICAL ANTIDEPRESSANT"

ATYPICAL ANTIDEPRESSANT

• MOA: BLOCKS THE FOLLOWING...
• ALPHA-2 (Gi COUPLED) RECEPTORS
• 5HT-2A&C (Gq COUPLED)
• 5HT-3 (LG IONOTROPIC)
• H1 (Gq COUPLED) -CAUSING POSSIBLE UNWANTED SOMNOLENCE

• NOT A REUPTAKE INHIBITOR!
• BLOCKING THE 5HT-3 RECEPTOR STOPS ANY POSSIBLE NAUSEA OR VOMITING

REMERON

ATYPICAL ANTIDEPRESSANT

MOA: MODERATELY BLOCKS REUPTAKE BY DAT (DOPAMINE TRANSPORTER), THEREBY LEAVING MORE DA IN THE SYNAPSE TO ACT ON THE POSTSYNAPTIC CELL

WELLBUTRIN, APLENZIN, ZYBAN

METABOLIZED INTO AMPHETAMINE LIKE PRODUCTS, WHICH CAUSE THE TYPICAL SIDE EFFECTS SUCH AS AGITATION, ANOREXIA, INSOMNIA, AND EVEN SEIZURES AT HIGH DOSES

ATYPICAL ANTIDEPRESSANT

• MOA:
• -WEAK SSRI
• -BLOCKS PRE-SYNAPTIC 5HT-1(Gi), WHICH INHIBITS INHIBITION OF 5HT
• -BLOCKS 5HT-2(Gq) RECEPTORS
• -ITS METABOLITE mCPP BLOCKS 5HT-2 RECEPTORS AS WELL

DESYREL

SIDES EFFECTS CAN INCLUDE MILD SEDATION BY H1 BLOCKAGE, AND ORTHOSTATIC HYPOTENSION AND PRIAPISM DUE TO SOME ALPHA-1 BLOCKAGE

ATYPICAL ANTIDEPRESSANT

• MOA:
• -WEAK SNRI
• -5HT-2 (Gq COUPLED) BLOCKER
• -ITS METABOLITE mCPP ALSO BLOCKS 5HT-2 (Gq COUPLED) RECEPTORS

NO NAME BRAND

ALMOST SAME AS TRAZODONE EXCEPT IT'S A WEAK SNRI INHIBITOR INSTEAD OF JUST WEAK SSRI INHIBITOR, AND IT DOES NOT BLOCK PRE-SYNAPTIC 5HT-1

NOT NEARLY AS PRESCRIBED AS TRAZODONE DUE TO VARIOUS TOXICITY ISSUES

NON SELECTIVE MAOI

MOA: ACTS AS AN IRREVERSIBLE SUBSTRATE INHIBITOR OF MAO, THEREBY PERMANENTLY ENDING THE ACTIONS OF MAO UNTIL THE BODY GENERATES MORE WEEKS LATER. THIS EVENTUALLY LEADS TO A BUILD UP OF 5HT, DA, AND NE, WHICH ALL CAN ACT ON RESPECTIVE RECEPTORS TO CONTRIBUTE TO ELEVATED MOOD BY VARIOUS MECHANISMS.

PARNATE

5-10 DAYS REQUIRED FOR MAX MAOI

DISCLAIMER: SADLY YOU MUST AVOID BEER, WINE, AND CHEESE WHILE ON THIS BECAUSE THEY CONTAIN TYRAMINE, WHICH WOULD NORMALLY BE METABOLIZED BY MAO IN THE GI, BUT WHEN TYRAMINE GETS INTO THESE ADRENERGIC CELLS WITH NO MAO AROUND TO METABOLIZE IT, IT PUSHES ALL THE NE OUT INTO THE SYNAPSE CAUSING SYMPATHETIC MADNESS KNOWN AS HYPERTENSIVE CRISIS, OR MORE SCIENTIFICALLY THE CHEESE EFFECT.

NON SELECTIVE MAOI

MOA: ACTS AS AN IRREVERSIBLE SUBSTRATE INHIBITOR OF MAO, THEREBY PERMANENTLY ENDING THE ACTIONS OF MAO UNTIL THE BODY GENERATES MORE WEEKS LATER. THIS EVENTUALLY LEADS TO A BUILDUP OF 5HT, DA, AND NE, WHICH ALL CAN BE RE-RELEASED INTO THE SYNAPSE TO ACT ON THEIR RESPECTIVE RECEPTORS, WHICH CAN ELEVATE MOOD BY VARIOUS MECHANISMS.

NARDIL

5-10 DAYS REQUIRED FOR MAX MAOI

DISCLAIMER: SADLY YOU MUST AVOID BEER, WINE, AND CHEESE WHILE ON THIS BECAUSE THEY CONTAIN TYRAMINE, WHICH WOULD NORMALLY BE METABOLIZED BY MAO IN THE GI, BUT WHEN TYRAMINE GETS INTO THESE ADRENERGIC CELLS WITH NO MAO AROUND TO METABOLIZE IT, IT PUSHES ALL THE NE OUT INTO THE SYNAPSE CAUSING SYMPATHETIC MADNESS KNOWN AS HYPERTENSIVE CRISIS, OR MORE SCIENTIFICALLY THE CHEESE EFFECT.

SELECTIVE MAOI (FOR B) AT LOW DOSES

NON-SELECTIVE MAOI AT HIGHER DOSES

MOA: ACTS AS AN IRREVERSIBLE SUBSTRATE INHIBITOR OF MAO, THEREBY PERMANENTLY ENDING THE ACTIONS OF MAO UNTIL THE BODY GENERATES MORE WEEKS LATER. THIS WILL EVENTUALLY LEAD TO INTRA-CELLULAR BUILDUP OF 5HT, DA, AND NE, WHICH WILL ALL EVENTUALLY ACT ON THEIR RESPECTIVE RECEPTORS ON PRE-SYNAPTIC CELLS TO ELEVATE MOOD BY VARIOUS MECHANISMS.

ELDEPRYL, EMSAM(TRANSDERMAL)

5-10 DAYS REQUIRED FOR MAX MAOI

DISCLAIMER: SADLY YOU MUST AVOID BEER, WINE, AND CHEESE WHILE ON THIS BECAUSE THEY CONTAIN TYRAMINE, WHICH WOULD NORMALLY BE METABOLIZED BY MAO IN THE GI, BUT WHEN TYRAMINE GETS INTO THESE ADRENERGIC CELLS WITH NO MAO AROUND TO METABOLIZE IT, IT PUSHES ALL THE NE OUT INTO THE SYNAPSE CAUSING SYMPATHETIC MADNESS KNOWN AS HYPERTENSIVE CRISIS, OR MORE SCIENTIFICALLY THE CHEESE EFFECT.

COMBO ANTIDEPRESSANT THERAPY

• OLANZAPINE MOA: 2ND GENERATION THIENOBENZO ANTIPSYCHOTIC WHICH STRONGLY BLOCKS THE FOLLOWING:
• 5HT-2A&C
• D1 THROUGH D4
• H1
• ALPHA-1
• -MODERATELY BLOCKS:
• 5HT-3
• M1 THROUGH M5
• GABAa (BZD)
• BETA RECEPTORS

FLUOXETINE MOA: SSRI

OLANZAPINE + FLUOXETINE SEEMS TO HAVE A SYNERGISTIC EFFECT

SYMBYAX