title: Effect of pimozide on the increase of muscarinic receptors caused by mazindol and apomorphine in the rat cerebral motor cortex.
abstract: The effects of pimozide, mazindol and apomorphine on muscarinic receptors in homogenates of rat cerebral motor cortex were measured by binding assays, using 3H-N-methylscopolamine (3H-NMS) alone as ligand (for the measurement of M1- and M2-like receptors) or in the presence of carbachol or pirenzepine for determination of M1- and M2-like receptors, respectively. Female Wistar rats (150 g) were treated daily for one week with pimozide, a dopaminergic antagonist (10 and 20 mg/kg, po, by gavage), or with apomorphine (1 mg/kg, ip). In another set of experiments, animals were treated with pimozide and 30 min later with mazindol (10 mg/kg, po, by gavage) or apomorphine. The drugs were administered daily for one week. Controls received the same volume of saline. 3H-NMS binding was increased from the control value of 418 +/- 17 to 548 +/- 42 fmol/mg protein by administration of mazindol (10 mg/kg) but binding was reduced to 360 +/- 11 fmol/mg protein upon administration of pimozide (20 mg/kg) plus mazindol (10 mg/kg). Similarly 10 mg/kg pimozide reduced the increase in M1-like receptors caused by mazindol from 262 +/- 31 to 220 +/- 20 fmol/mg protein. Although 20 mg/kg pimozide alone produced a decrease in M1- plus M2-like receptors (from 418 +/- 17 to 348 +/- 22 fmol/mg protein), its action was preferentially on M2-like receptors, decreasing them from 148 +/- 10 to 111 +/- 15 fmol/mg protein in the control and treated groups, respectively. At the higher dose, 20 mg/kg pimozide also inhibited the 3H-NMS binding (M1- plus M2-like receptors) in the presence of apomorphine (263 +/- 25 vs 418 +/- 17 fmol/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors.forename: F C
authors.initials: FC
authors.lastname: de-Sousa
authors.forename: M M
authors.initials: MM
authors.lastname: Marinho
authors.forename: G V
authors.initials: GV
authors.lastname: Aguiar
authors.forename: G S
authors.initials: GS
authors.lastname: Viana
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D008454:Mazindol / Q000494:pharmacology*; D009044:Motor Cortex / Q000502:physiology*; D010868:Pimozide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic / Q000187:drug effects*
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D010868:Pimozide; D008454:Mazindol; D001058:Apomorphine