FUNCTIONAL COMPARISON BETWEEN NUVENZEPINE AND PIRENZEPINE ON DIFFERENT GUINEA-PIG ISOLATED SMOOTH-MUSCLE PREPARATIONS

The antimuscarinic agents nuvenzepine and pirenzepine were tested on four guinea pig isolated smooth muscle preparations in order to better investigate the existence of differences in the functional activities of such antagonists, as suggested by previous reports. The effects of both compounds were compared to those of atropine. Nuvenzepine showed a four-fold higher affinity than pirenzepine in competitively antagonizing acetylcholine-induced contractions on isolated ileal musculature (pA(2)=7.08+/-0.15) and on longitudinal ileum dispersed cells (pA(2)=7.11+/-0.19). By contrast, unlike pirenzepine which was ineffective, nuvenzepine inhibited histamine-induced ileal. motor activity in a dualistic manner, behaving as an irreversible competitive H-1 antagonist (pA(2)=5.02+/-0.11). Nuvenzepine was almost equipotent to pirenzepine in competitively preventing bethanechol-induced gall-bladder contractions (pA(2)=7.23+/-0.16) and it displayed a four-fold higher potency than pirenzepine in blocking vagal-stimulated tracheal constrictions (pIC(50)=6.77+/-0.06). Both compounds were definitely less potent than atropine. On the whole, these findings indicate that, on the selected preparations, nuvenzepine substantially shares the antimuscarinic properties of pirenzepine but it is also endowed with a (weak) H-1-blocking action. Furthermore, based on some observations, the presence in gallbladder smooth muscle of muscarinic receptors distinguishable from those of ileum could be speculated.