Neuropharmacology

Agonists

enhance potency of neurotransmitter; cholinergic agonists=parasympathomimetic; adrenergic agonists=sympathomimetic

Antagonists

reduce effectiveness; cholinergic antagonists=sympathomimetic; adrenergic antagonists=parasympathomimetic

ACh

primary class of neurotransmitters; agonists=nicotine, donepezil; antagonists=curare, botulin, atropine

NE

primary class of neurotransmitters; agonists=amphetamine, atomoxetine, methylphenidate; antagonists=propranolol

Donepezil

ACh+; used to manage Alzheimer’s disease; cholinesterase inhibitor (increases availability of acetylcholine in the brain); side effects: fatigue, diarrhea

Nicotine

ACh+; stimulant drug; binds to nicotinic acetylcholine receptors (nAChRs); nicotinic receptors are widely distributed in the brain, including the Ventral Tegmental Area (VTA), key part of the reward system; activation of nAChRs on VTA dopamine neurons increases dopamine release in the nucleus accumbens and prefrontal cortex; highly addictive due to strong dopaminergic reinforcement

Atropine

ACh-; anticholinergic (blocks parasympathetic function); muscarinic ACh receptor antagonist; produces sympathomimetic-like effects because it inhibits parasympathetic tone; dilates pupils (mydriasis), reduces secretions (salivary, respiratory), treats bradycardia, helps manage hypotension during surgery by blocking excessive vagal tone

Curare

ACh-; blocks nicotinic acetylcholine receptors at the neuromuscular junction; causes muscular relaxation; leads to flaccid paralysis including respiratory muscles; historically used as a poison, modern derivatives used in anesthesia; basis for agents used in lethal injection protocols

Botulinum Toxin (Botox)

ACh-; blocks ACh release causing muscle relaxation; used cosmetically to remove wrinkles and medically to reduce sweating (blocks ACh at sweat glands); cleaves SNARE proteins required for synaptic vesicle fusion; without SNAREs → no ACh release → flaccid paralysis; effects last weeks to months until new synaptic terminals form

Amphetamines

NE+; CNS stimulants; strong sympathomimetics; FDA-approved forms (adderall, desoxyn) used for ADHD and obesity; high potential for abuse and dependence due to dopamine release; side effects: nervousness, insomnia, dry mouth, loss of appetite, increased heart rate/blood pressure

Methylphenidate (Ritalin)

NE+; sympathomimetic/CNS stimulant; dopamine and norepinephrine reuptake inhibitor (blocks DAT and NET); mild adrenergic receptor agonist effects; used to treat ADHD and narcolepsy; improves attention span, alertness, and executive function; side effects: insomnia, tachycardia, decreased appetite, nervousness

Atomoxetine (Strattera)

NE+; non-stimulant, used for ADHD, selective norepinepherine reuptake inhibitor (SNRI); no abuse potential (not a controlled substance); side effects: dry mouth, reduced appetite, constipation, mild eavaluated heart rate/blood pressure

Propranolol (Inderal)

Adrenergic receptor antagonist (non-selective beta-blocker); used for anxiety, migraines/headaches, hypertension, and tremor; prevents stage-fright symptoms (blocks tachycardia, tremor, sweating), functionally parasympathomimetic by blocking sympathetic beta-effects; beta-blocker class medication

Dopamine

important neurotransmitter; agonists=levodopa, amphetamine, methylphenidate, cocaine; antagonists=haloperidol

Seratonin

important neurotransmitter; agonists=fluoxetine, LSD

GABA

brain’s primary inhibitory neurotransmitter; agonists=BZDs, ethanol

Levodopa (L-DOPA)

DA+; precursor of dopamine (crosses the blood-brain barrier and is converted to dopamine in the brain); used to treat Parkinson’s disease; effect is temporary/limited over time because chronic dopamine replacement leads to down-regulation of dopamine receptors and progression of neuron loss; not addictive because it raises dopamine slowly and mainly in motor pathways, not in the brain’s reward system

Mesolimbic System

the “reward” system of the brain; most dopamine neurons originate in two neighboring areas of the midbrain, the VTA and SN

VTA

part of the mesolimbic system in the midbrain; gives rise to two of the major dopamine pathways, one projecting to the frontal cortex (mesocortical pathway) and the other to the nucleus accumbens (mesolimbic pathway)

SN

part of the mesolimbic system in the midbrain; dopamine neurons in the SN porject to the striatum (nigrostriatal pathway)

Cocaine

DA+; a powerful CNS stimulant; high potential for addiction

Amphetamine

increases synaptic dopamine and norepinephrine concentrations, but does so by enhancing the release of neurotransmitters into the synapse

Haloperidol (Haldol)

DA-; dopamine receptor antagonists (strong D2 blocker); antipsychotic used to treat schizophrenia and acute psychosis; can cause Parkinson’s-like side effects

Fluoxetine (Prozac, Paxil, Zoloft, Celexa, Lexapro)

Sert+; antidepressant; low levels of seratonin are associated with depression; Selective Serotonin Reuptake Inhibitor (SSRI); result in increased serotonin levels in the synaptic cleft; mechanism similar in principle to cocaine, but specific to serotonin (blocks SERT only, not DA/NE)

LSD (Lysergic Acid Diethylamide)

Sert+; powerful psychedelic/hallucinogen; extremely potent (active at microgram doses); seratonin recepter agonist, especially 5-HT2A; produces the characteristic “acid trip”; acts on raphe nuclei (serotonin system) and cortex (sensory/cognitive effects); similar psychedelics include psilocybin, DMT, and mescaline; not addictive

Benzodiazepines (BZDs) (Valium, Xanax)

GABA+; GABA agonists that bind to the GABA- receptor; increase frequency of Cl- channel opening; produce sedative, hynotic, anxiolytic effects by depressing CNS activity; indirectly increase dopamine release, making them highly addictive; dangerous when combined with alcohol (both depress respiration)

Ethanol (alcohol)

GABA+; CNS depressant; GABA receptor agonist; increases dopamine release → euphoria/relaxation (high addiction potential); #1 drug problem in the USA; dangerous interactions with benzodiazepines (addictive respiratory depression); rapidly absorbed; impairs cognition first, then motor control