Central inhibitory effects of pirenzepine
Abstract
The new selective M1 receptor blocking agent pirenzepine (PZ, l, 2.5 and 5 mg/kg, ip) decreased spontaneous motor activity of mice. This effect was antagonized by physostigmine (0.5 mg/kg, ip). In rabbits PZ (0.25, 0.5, l and 2 mg/kg, icv) changed EEG from low voltage rapid wave to high voltage slow wave. Larger doses made this effect more prominent and caused loss of righting reflex. The inhibitory effect of PZ on CNS could be antagonized by pilocarpine (2.5 mg/kg, icv).
PZ (0.25-1 mg/kg, icv) caused increase in respiratory frequency and decrease of heart rate. Similar effects could also be induced by pilocarpine (2.5 mg/kg, icv). Nevertheless, PZ in combination with pilocarpine had no such effects, showing that there existed an antagonism between the two drugs taking place in CNS. On the contrary, 4 mg/kg PZ, (icv) inhibited respiration. Our results suggest that the central inhibitory action of PZ is anticholinergic in blocking M1 receptor and its effects on respiration and heart rate might be related to central cholinergic mechanism in some way.
Keywords:
PZ (0.25-1 mg/kg, icv) caused increase in respiratory frequency and decrease of heart rate. Similar effects could also be induced by pilocarpine (2.5 mg/kg, icv). Nevertheless, PZ in combination with pilocarpine had no such effects, showing that there existed an antagonism between the two drugs taking place in CNS. On the contrary, 4 mg/kg PZ, (icv) inhibited respiration. Our results suggest that the central inhibitory action of PZ is anticholinergic in blocking M1 receptor and its effects on respiration and heart rate might be related to central cholinergic mechanism in some way.