1. Neurotransmitters

2. CRITERIA NT found in axon terminals NT released by action potentials
Synthesis identified
External application mimic normal Response
Pharmacology same for normal and externally applied NT ~

3. Lock & Key Model NT binds to receptor NT = key Receptor = lock
Receptor changes shape
determines if EPSP or IPSP
receptor subtypes
NOT NT ~

4. ligand binds to receptor activation: + or - ~NT
Receptor A

5. Same NT can bind to different -R different part of NT ~
Receptor A
Receptor B

6. Specificity of drugs
Drug B
Drug A NT
Receptor A
Receptor B

7. Acetylcholine - ACh Most abundant NT in Peripheral N.S.
also found in Central N.S.
Precursor = choline
nutrient
Degraded by acetylcholinesterase-
AChE
Membrane bound - pre- & postsynaptic
Nicotinic receptor - ionotropic
Muscarinic receptor - metabotropic ~

8. Acetylcholine Synthesis
acetyltransferase
choline
+ acetyl CoA
ACh + CoA

9. Ach - Distrubution Peripheral N.S. Excites somatic muscle Autonomic NS
Ganglia
Parasympathetic NS Neuroeffector junction
Central N.S. - widespread
Hippocampus
Hypothalamus ~

10. Cholinergic Agonists Direct Muscarine Nicotine small doses Indirect
AChE Inhibitors ~

11. AChE inhibitors Physostigmine Organophosphates - irreversible
DFP (Diisopropyl Fluoroph osphate)
Soman & Sarin
Malathion*
Agonist or Antagonist?
indirect agonist ~

12. Cholinergic Antagonists
Direct
Nicotinic - Curare
Muscarinic - Atropine
Scopolamine
Indirect
Botulinum Toxin
Black Widow Spider Venom ~

13. ACh A
Botulinum toxin
BWSV
curare atropine
AChE
AChE N M

14. Monamines Amino acid precursors single amine group 2 groups
Catecholamines - catechol ring
Indolamine - indole ring
Affected by many of same drugs ~

15. Monoamines Catecholamines Dopamine - DA Dopaminergic
Norepinephrine - NE
Noradrenergic
Epinephrine - E
Adrenergic ~
Indolamines
Serotonin - 5-HT
Serotonergic

16. Monoamines Terminated by... reuptake monoamine oxidase - MAO
catechol-O-methyltranferase - COMT
also in liver
Reserpine ---> leaky vesicles
depletes monoamines ~

17. Monoamines
MAO
Reserpine A
COMT
MAO

18. Indirect Monoamine Agonists
MAOIs
Iproniazid,selegiline,moclobemide
Reuptake blockers
Tricyclic antidepressants
Imipramine
Desipramine
Cocaine & Amphetamine ~

19. Dopamine Only in central nervous system mostly inhibitory systems
Reward
Schizophrenia
Movement
Nigrostriatal Pathway
At least 5 DA-R types: D1, D2, etc. ~

20. Dopaminergic Drugs Agonist L-dopa Antagonists Chlorpromazine
Haloperidol
D ~

21. Dopamine Synthesis Tyrosine DOPA DA tyrosine DOPA hydroxylase
decarboxylase
Tyrosine
DOPA DA
DOPA: dihydroxy phenylealanine

22. Norepinephrine Peripheral N.S. Sympathetic neuroeffector junction
Adrenal glands
Central N.S.
Hypothalamus
Locus coeruleus
Alpha & Beta receptor subtypes
NEa & NEb ~

23. Noradrenergic Drugs Agonists Mescaline Ephedrine Antagonist
Propranalol -
beta receptors ~

24. Norepinephrine Synthesis
tyrosine
hydroxylase
DOPA
decarboxylase
dopamine
b hydroxylase
Tyrosine
DOPA DA NE

25. Serotonin NOT a catecholamine Peripheral 98% in blood & smooth muscle
Central N.S.
Raphe nucleus
Hypothalamus
R subtypes: 5HT1 & 5HT2 ~

26. Sertonergic Drugs Agonists SSRIs Buspirone
Selective Serotonin Reuptake Inhibitors (fluxoteine, sertraline, paroxetine….)
Buspirone
MDMA (3,4-methylenedioxymethamphetamine)
Ecstacy ~

27. Sertonergic Drugs Antagonists Psilocybin
LSD (Lysergic acid diethylamide) in CNS
Inverse agonist
ketanserin ~

28. Serotonin Synthesis 5-HT Tryptophan 5-HTP tryptophan 5-HTP hydroxylase
decarboxylase
Tryptophan
5-HTP
5-HT
HTTP: hydroxytryptophan, HT: hydroxytryptamine

29. Gamma-aminobutyric acid
GABA - GABAergic
Major NT in brain inhibitory system
Receptor subtypes
GABAA - controls Cl- channel
GABAB - controls K+ channel
Precursor = glutamate ~

30. GABAergic Drugs ß CCM ~ Ro 15-4513 Agonists Benzodiazepines
Barbiturates
Ethyl alcohol (ETOH)
Antagonists
Picrotoxin
Inverse agonist Ro
ß CCM ~
CCM: carboline-3-carboxylate

31. GABA Synthesis & Reuptake
From Krebs cycle
metabolism of glucose
in mitochondria
From Glial cells
GABA ---> Glutamate ---> Glutamine Glutamine into neurons
After release
GABA back into glia ~

32. GABA Synthesis
glutamic acid
decarboxylase
Glutamate
GABA

33. Neuropeptide Chains of amino acids Synthesis in soma
Often neuromodulators
alters sensitivity of neurons
slower, longer-lasting effects
Substance P - pain signaling
Endorphins - analgesia, euphoria ~

34. Endorphins Opioids Dynorphin leu-enkephalin Beta-endorphin
met-enkephalin
leu-enkephalin
Beta-endorphin
Receptor subtypes:
mu1, mu2, kappa, delta, omega ~

35. Endorphins (cont.) Agonists morphine heroin codeine Antagonists
naloxone
naltrexone ~

36. Other NTs Excitatory amino acids Glutamate & Aspartate Histamine
Inflammatory Response
Nitric Oxide - It’s a gas
Carbon Monoxide?
Anandamide
ligand for THC-R ~
THC: Tetrahydrocannabinol