Basic Lecture Outline with Notes

CHAPTER 4 Psychopharmacology Basic Lecture Outline with notes Principles of Psychopharmacology Definition of drug Exogenous Endogenous Pharmacokinetics Routes of administration (seven ways drugs can be administered) Drug Effectiveness Dose-response curve Margin of safety/therapeutic index Effects of Repeated Administration Tolerance Sensitization Placebo Effects

Sites of Drug Action Effects on Production of Neurotransmitters Agonist (example: L-Dopa precursor of dopamine and norepinephrine) Antagonist (example: PCPA blocks tryptophan from becoming 5-HT) Effects on Storage and Release of Neurotransmitters Filling of neurotransmitter into vesicle Antagonist –Blocks filling of neurotransmitter into vesicle (example: reserpine) Release of neurotransmitter from terminal button Antagonist – Prevents release of neurotransmitter (example: Botulinum toxin) Agonist – triggers release of neurotransmitter (example: Black widow spider venom) Effects on Receptors Autoreceptor Antagonists - stimulates autoreceptor- thus inhibits synthesis and release of neurotransmitter (example: apomorphine) Agonists – blocks autoreceptors – drug increases synthesis and release of nuerotransmitter (example: clonadine)

Binding sites Agonist – masquerades as the neurotransmitter by binding with the same site – (example: muscarine/nicotine) Antagonists-masquerades as neurotransmitter, but blocks the site – (example: atropine/curare) Effects on Reuptake or Destruction of Neurotransmitters Agonist - Leaves more neurotransmitter in synaptic cleft where it can stimulate postsynaptic receptors (example: SSRI’s Prozac, Paxil, Zoloft) Agonist – Destroys the enzyme which would deactivate the neurotransmitter Acetylcholine (example: AchE)

Neurotransmitters and Neuromodulators

Acetylcholine - primary neurotransmitter – generally excitatory - all muscle movement due to release of Ach Dorsolateral pons – REM sleep Basal forebrain – activates cerebral cortex and facilitates learning Medial septum – controls the electrical rhythms of hippocampus and includes the formation of particular kinds of memories

The Monoamines (neurons serve to modulate the function of widespread regions of brain) Catecholamine Epinephrine – hormone secreted by adrenal medulla – can also serve as neurotransmitter in brain Norepinephrine – increases vigilance – attentiveness to environment Dopamine (can generate excitatory and inhibitory postsynaptic potentials depending on postsynaptic receptors.) Nigrostriatal system – substantial nigra – neostriatum the caudate nucleus and putamen (control of movement) Mesolimpic system – ventral tegmental area – nucleus accumbens, amygdale, hippocampus – (addiction) Mesocortical system – ventral tegmental – prefrontal cortex – (short-term memory, planning problem solving) Indolamines Serotonin (5-HT) – regulates mood, controls eating, sleep and arousal and also used in regulation of pain. Amino Acids Most synaptic communication is accomplished by two neurotransmitters; EPSP effects Glutamate the principal excitatory neurotransmitter in brain and spinal cord Glutamate receptors Ionotropic NMDA receptor Permits sodium and calcium to enter cell. Generates ESPS. Calcium serves as second messenger, very important in forming memory. AMPA receptor Most common glutamate receptor controls sodium channel products ESPS Kainate receptor Similar to AMPA receptor controls kainic acid Metobotropic glutamate receptor

IPSP effects GABA generally inhibitory GABA (a) is ionotropic Five binding sites GABA Benodiazephine (tranquilizers) Barbiturates and alcohol Picrotoxin (opposite of benzodiazepine and barbiturate) GABA (b) is metabotropic opens potassium channels hyperpolarizing IPSP’s ( Glycine (found in spinal cord and lower brain stem)

Peptides Endogenous opiads “like opium” found in midbrain (tectum, tegmentum, periaquductal gray) Produces analgesia Inhibits fleeing and hiding Produces “reward” or reinforcement Lipids Cannabinoids THC (analgesia and sedation, stimulates appetite, reduces nausea, reduces symptoms of certain motor disorders.)

Nucleosides Adenosine (ribose and adenine) release by glial cells and neurons when cells are short of fuel or oxygen. Adenosine opens potassium channels producing IPSP’s. Caffeine blocks adenosine receptors. Soluble Gases Nitric oxide – soluable gas produced by activity of an enzyme found in certain neurons. Dilates blood vessels in regions of the brain that become metabolically active.