Page 390 - Basic _ Clinical Pharmacology ( PDFDrive )

376 SECTION V Drugs That Act in the Central Nervous System

TABLE 21–2 Summary of neurotransmitter pharmacology in the central nervous system.

Receptor Subtypes
Transmitter Anatomy and Preferred Agonists Receptor Antagonists Mechanisms
+
Acetylcholine Cell bodies at all levels; Muscarinic (M 1 ): Pirenzepine, atropine Excitatory: ↓ in K conductance;
long and short connections muscarine ↑ IP 3 , DAG
+
Muscarinic (M 2 ): Atropine, methoctramine Inhibitory: ↑ K conductance;
muscarine, bethanechol ↓ cAMP
Motoneuron-Renshaw cell Nicotinic: nicotine Dihydro-β-erythroidine, Excitatory: ↑ cation conductance
synapse α-bungarotoxin
Dopamine Cell bodies at all levels; D 1 : dihydrexidine Phenothiazines Inhibitory (?): ↑ cAMP
short, medium, and long
connections
2+
D 2 : bromocriptine Phenothiazines, Inhibitory (presynaptic): ↓ Ca ;
+
butyrophenones Inhibitory (postsynaptic): ↑ in K
conductance, ↓ cAMP
–
GABA Supraspinal and spinal GABA A : muscimol Bicuculline, picrotoxin Inhibitory: ↑ Cl conductance
interneurons involved
in pre- and postsynaptic
inhibition
2+
GABA B : baclofen 2-OH saclofen Inhibitory (presynaptic): ↓ Ca
conductance; Inhibitory
+
(postsynaptic): ↑ K conductance
Glutamate Relay neurons at all levels N-Methyl-d-aspartate 2-Amino-5- Excitatory: ↑ cation conductance,
and some interneurons (NMDA): NMDA phosphonovalerate, particularly Ca 2+
dizocilpine
AMPA: AMPA NBQX Excitatory: ↑ cation conductance
Kainate: kainic acid, ACET Excitatory: ↑ cation conductance
domoic acid
2+
Metabotropic: ACPD, MCPG Inhibitory (presynaptic): ↓ Ca
quisqualate conductance, ↓ cAMP; Excitatory:
+
↓ K conductance, ↑ IP 3 , DAG
–
Glycine Spinal interneurons Taurine, β-alanine Strychnine Inhibitory: ↑ Cl conductance
and some brain stem
interneurons
+
5-Hydroxytryptamine Cell bodies in mid-brain 5-HT 1A : eptapirone Metergoline, spiperone Inhibitory: ↑ K conductance,
(serotonin) and pons project to all ↓ cAMP
levels
+
5-HT 2A : LSD Ketanserin Excitatory: ↓ K conductance,
↑ IP 3 , DAG
5-HT 3 : 2-methyl-5-HT Ondansetron Excitatory: ↑ cation conductance
+
5-HT 4 : cisapride Piboserod Excitatory: ↓ K conductance
+
Norepinephrine Cell bodies in pons and α 1 : phenylephrine Prazosin Excitatory: ↓ K conductance,
brain stem project to all ↑ IP 3 , DAG
levels
2+
α 2 : clonidine Yohimbine Inhibitory (presynaptic): ↓ Ca
+
conductance; Inhibitory: ↑ K
conductance, ↓ cAMP
+
β 1 : isoproterenol, Atenolol, practolol Excitatory: ↓ K conductance,
dobutamine ↑ cAMP
β 2 : albuterol Butoxamine Inhibitory: may involve ↑ in elec-
trogenic sodium pump; ↑ cAMP
+
Histamine Cells in ventral posterior H 1 : 2(m-fluorophenyl)- Mepyramine Excitatory: ↓ K conductance,
hypothalamus histamine ↑ IP 3 , DAG
+
H 2 : dimaprit Ranitidine Excitatory: ↓ K conductance,
↑ cAMP
H 3 : R-α-methyl-histamine Thioperamide Inhibitory autoreceptors
(continued)