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 (150g) were treated daily for one week with pimozide, a dopaminergic antagonist (10 and 20 mg/Kg, po, by gavage), or with apomorphine (1mg/Kg,ip). In another ser 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 ñ 17 ñ 42 fmol/mg protein by administration of mazindol (10mg/Kg) but binding was reduced to 360 ñ 11 fmol/mg protein upon administration of pimozide (20mg/Kg) plus mazindol (10mg/Kg. Similarly 10 mg/ Kg pimozide reduced the increase in M1-like receptors caused by mazindol from 262 ñ to 220 ñ 20 fmol/mg protein. Although 20 mg/Kg pimozide alone produced a decrease in M1-plus M2-like receptors (from 418 ñ 17 to 348 ñ 22 fmol/mg protein), its action was preferentially on M2-like receptors, decreasing them from 148 ñ 10 to o ñ 15 fmol/mg protein in the control and treated groups, respectively. At the higher dose, 20 mg/Kg pimozide also inhibited the 3 H-NMS binding (M1-plus M2-like receptors) in the presence of apomorphine (263ñ25 vs 418 ñ 17 fmol/mg protein...