title: The actions of antipsychotic drugs on dopamine receptors in the rat substantia nigra.
abstract: The activity of neurones in the zona compacta of the rat substantia nigra was recorded extracellularly in vitro. Dopamine produced a dose-dependent depression of firing, threshold doses being in the 3 microM range. The inhibitory effects of dopamine were antagonized by (-)-sulpiride (pA2 7.5), haloperidol (pA2 8.4) and cis-flupenthixol (pA2 6.9). The actions of gamma-aminobutyric acid (GABA) were not affected by these compounds. The gradients of Schild plots of data for (-)-sulpiride were less than unity while those for haloperidol and cis-flupenthixol were greater than unity, which suggests that the antagonism was not competitive. This is discussed with regard to the use of a bioassay system in the analysis of the effects of antagonists. Haloperidol and (-)-sulpiride were found to have similar potencies, as dopamine receptor antagonists, to those predicted from biochemical and clinical efficacy studies, but cis-flupenthixol was less potent than expected.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D005475:Flupenthixol / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism; D013378:Substantia Nigra / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013469:Sulpiride; D005475:Flupenthixol; D006220:Haloperidol; D004298:Dopamine