1. Psychopharmacology The Study of the effects of drugs on the nervous system and behavior Drugs: – Exogenous chemical (not produced by the body) – Not necessary for normal functioning Not a vitamin, mineral, protein, carbs… – Alters the functions of certain cells (neurons) – when given in low doses (mg/kg)

2. Drug influence: Changes in physiological and behavioral processes of the organism Action sites: Sites where the drug

3. 1. Form of drug administration (how it is taken) 2. Drug fate in body Principles of psychopharmacology include:

4. 1. Forms of drug administration: 1.Intravenous injection 2.Intraperitoneal injection 3.Intramuscular injection 4.Subcutaneous injection 5.Oral administration 6.Sublingual administration 7.Intrarectal administration 8.Inhalation 9.Topical administration 10.Intracereberal administration

5. Drugs get to the brain usually through the blood

6. 2. Fate of drug Depot Binding with Blood Albumin Protein Can influence the rate at which the drug will reach the brain from the blood stream

7. Drug efficacy Dose-response curve – describes the influence of a drug as a function of the dose administered

8. Multiple effects of drugs (beneficial effects, and side effects)

9. The separation between the two curves serves as an measure for its safety Therapeutic Index = LD 50 /ED 50 LD – Lethal dose ED – effective dose Examples: Morphine (muscle relaxant) has a TI of 70 Cocaine: 15 Heroin: 6 Alcohol: 10 (but you usually vomit/pass out before reaching the lethal dose)

10. Drug effectiveness depends on: Site of action Affinity & kinetics Number of times it was used: Tolerance = Decrease in the efficiency of a drug Sensitization = Increase in the efficiency of a drug

11. Once a drug enters the brain it may have one of two effects: Agonist – mimics/facilitates the post-synaptic effect Antagonist – inhibits/blocks the post synaptic effect for a given neurotransmitter

12. Drugs can affect any stage in the process of synaptic transmission: 1)Production of neurotransmitter 2)Packing in vesicles and vesicle release 3)Binding to receptors 4)Neurotransmitter degradation and reuptake

13. Production of neurotransmitter 1.Precursor of neurotransmitter (Agonist): Dopamine L-DOPA serves as a precursor for the production of dopamine (used in Parkinson’s Disease) Glutamate MSG (monosodium glutamate) – is a precursor of glutamate production 2. Inactivation of an enzyme needed for synthesis (Antagonist) AMPT (Alpha-methyl-p-tyrosine) – blocks Tyrosine hydroxylase (Antagonist)

14. serotonin p-chlorophenylalanine (PCPA) – is an inhibitor of Tryptophan hydroxylase

15. Storage and release of neurotransmitter 1.Preventing storage by inactivating vesicle transporter (Antagonist) Reserpine (blocks storage of norepinephrine, serotonin, and dopamine in the presynaptic vesicles) 2. Enhancing storage in vesicles by inhibiting neurotransmitter breakdown

16. 3. Stimulation of release from terminal button (Agonist) Black widow spider venom (facilitates release of AcH) 4. Inhibition of release from terminal button (Antagonist) Butulinium toxin (Botox) – blocks release of AcH

18. Post-synaptic receptors Direct agonists (competitive binding) – bind with receptor and activate it (mimic the effect of the neurotransmitter) – Examples: Nicotine, and Muscarine for AcH, LSD for serotonin Direct antagonist (competitive binding) – bind with the receptor and do not activate it (receptor blockers) – Examples: Curare (blocks the nicotinic AcH receptor) – Atropene (blocks the muscarinic AcH receptor) – Caffeine (blocks adenosine receptors)

19. Indirect agonist (non-competitive binding): Binds on a different site than the neurotransmitter but mimics its effect Indirect antagonist (non-competitive binding): Binds on a different site than the neurotransmitter and blocks its effect

20. A voltage and Neurotransmitter dependent channel PCP (angel dust): Indirect antagonist NMDA receptor (glutamate) PCP (angel dust) – indirect antagonist

21. GABAa Neurotransmitter dependent Cl- channel Indirect Agonists Reduce anxiety

22. Neurotransmitter degradation and reuptake 1.Blockers of re-uptake (agonists) Example: Cocaine is a seotonin-norepinephrine-dopamine reuptake inhibitor Hemicholine – blocks reuptake of choline and serves as an AcH antagonist Ritalin – inhibits reuptake of dopamine and norepinephrine Amphetamine (‘speed’) – inhibits reuptake of dopamine Fluoxetine (Prozac) – serotonine reuptake inhibitor (SSRI) MDMA (‘Ecstasy’) – NE and Serotonin transporters run backwards

23. 2. Blockers of neurotransmitter degradation (agonist): Example: Neostigmine inhibits AcH-Esterase (the enzyme that breaks AcH to Choline and Acetate) resulting in prolonged presence of AcH in synaptic cleft

24. Effects on pre-synaptic receptors Autoreceptors Stimulation Less release of neurotransmitter

25. Apomorphine (dopamine)