Nuvenzepine

Nuvenzepine is an mAChR antagonist previously in phase I clinical trials for the treatment of gastrospasm.

Nuvenzepine shows a four-fold higher affinity than pirenzepine in competitively antagonizing acetylcholine-induced contractions on isolated ileal musculature and on longitudinal ileum dispersed cells. Nuvenzepine is almost equipotent to pirenzepine in competitively preventing bethanechol-induced gall-bladder contractions and it displays a four-fold higher potency than pirenzepine in blocking vagal-stimulated tracheal constrictions[1].

Intraduodenally administration of Nuvenzepine displays a long-lasting and dose-dependent inhibition of neostigmine-induced intestinal motility in anaesthetized cats. On ileal motor activity, Nuvenzepine shows a potency 10 times greater than that of pirenzepine. Nuvenzepine is also active, unlike pirenzepine, on colonic stimulated motility. Furthermore, in conscious cats, Nuvenzepine inhibits pentagastrin-stimulated gastric acid secretion resulting 25-30 times more potent than pirenzepine[2]. Nuvenzepine has been found to be very active in inhibiting gastric acid secretion and intestinal hypermotility in rats, with very slight atropine-like side effects. The oral absorption rate is relatively slow, that the absolute bioavailability is 30 to 40%, that the elimination rate is slow and there is no accumulation in the body, and that there is very little metabolism[3].

[1]. Barocelli E, et al. Functional comparison between nuvenzepine and pirenzepine on different guinea pig isolated smooth muscle preparations. Pharmacol Res. 1994 Aug-Sep;30(2):161-70. [2]. Barocelli E, et al. Gastrointestinal activities of a new pirenzepine-analog, nuvenzepine, in the cat. Farmaco. 1990 Oct;45(10):1089-99. [3]. Caselli G, et al. Determination of nuvenzepine in human plasma by a sensitive [3H]pirenzepine radioreceptor binding assay. J Pharm Sci. 1991 Feb;80(2):173-7.