Effect of pimozide on the increase of muscarinic receptors caused by mazindol and apomorphine in the rat cerebral motor cortex

RESUMO

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...