4/9/11

Fundamentals of Psychopharmacology

Matt Schalles UCSD Cognitive Science [email protected]

Drugs of Interest

l Psycho Stimulants l l Caffeine l l Opiates l Endorphins l Alcohol l Everything l Marijuana l Endocannabiniods

Serotonin like l Hallucinogens - Catecholamine like - - dissociative

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Neurotransmitters of Interest

Amino Acids Biogenic Amines Neuropeptides Glutamate (Glu) Quaternary Amines Opioid Peptides GABA Acetylcholine (Ach) Enkephalins Monoamines Endorphins Catecholamines Dynorphins Dopamine (DA) Endomorphins Norepinephrine (NE) Indolamines (5-HT)

(Others: lipids & soluble gases)

Stimulant Drugs l Psychomotor Stimulants (Catecholamines)

- - (ritalin) - () l Cholinergic

- Nicotine l Adenosine

- caffeine

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Psychomotor stimulant kinetics

l Absorption l Half Lives

- Nasal membrane - Cocaine: 50-90 min

- stomach/intestinal - Methylphenidate: 3-4 hrs - Lungs - Amphetamines: 6-8 hrs - Bloodstream - < 12 hr

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Cocaine/Methylphenidate site of action

Amphetamine Site of action

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Medical Uses

l Obesity l Narcolepsy l ADHD l Local anesthetics/ vasoconstrictors

Caffeine

l Adenosine

- Ligand released by astrocyte

- Inhibits neurons - Competitive antagonist

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Opiates

l Opium l Endogenous opioids

- Morphine - Endorphins - Codeine - Endomorphins - Enkephalins - Dynorphins

Opiate Kinetics

l Absorption l Excreted by

- stomach/intestines 20-30 kidneys min

- Nasal membranes 5-8 min

- Bloodstream 15-30 sec - Lungs 7-10 sec l Metabolism

- 3-5 hr half-life - Liver enzymes

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Opioid Distribution

l 3 receptor types

- Mu - Delta - Kappa

Site of Action

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Opioid Antagonists

l Naloxone l Naltrexone

- High mu receptor - Similar binding profile affinity - Orally active Must be injected - - 4 hr half-life Short action (15-30 - - Induces withdrawal min)

Alcohol – the dirtiest of drugs

l Interacts with

- Glutamate

- GABA - Dopamine - Opiates - Serotonin - endocannabinoids

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Pharmacokinetics

l Absorption l Eliminated through

- Lipid soluble - Urine - Water soluble - Skin Lungs l Metabolism - - feces - Zero order - First pass - Second pass - alcohol-dehydrogenase

Net Alcohol effects?

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EtOH Sites of Action

l GABA

- Direct - Indirect agonist

Cannabinoids

l CB1 receptor

l Endocannabinoids

- 2-AG - anadamide

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Endocannabinoids

l Retrograde signaling

l Negative feedback mechanism

l Depolarization induced Suppression of Excitation

l DS inhibition

Hallucinogens

l Self Administration? l Psychedellics l Entheogens l Psychotomimetics

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Hallucinogens

l 3 Classes

- Serotonin-like - Catecholamine-like - Dissociative / Anesthetics

DMT

l Synthesized by mammals

l Dedicated Receptors in periphery

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Ayahuasca

Acetylcholine

st l 1 discovered

l 2 Receptors

- Nicotonic - Muscarinic

l Associated Functions

- Memory - Attention - Muscles

l Acetylcholine esterase

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Compounds Affecting Ach

l Nicotine l Amanita Muscaria l Crotoxin l Latrotoxin l Botulism

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