PINAVERIUM ACTS AS L-TYPE CALCIUM-CHANNEL BLOCKER ON SMOOTH-MUSCLE OFCOLON

The effect of pinaverium was electrophysiologically characterized and compared with the established L-type calcium channel blockers diltiaze m, D600, and nitrendipine on canine colonic circular smooth muscle. Ef fects were studied on the electrical activity of the smooth muscle cel ls, in particular the spontaneously occurring slow wave. In addition, effects were examined on spontaneous contraction patterns and contract ile activities generated by stimulation of cholinergic nerves or direc tly by stimulating muscarinic receptors. Effects were also examined on excitation of NO-releasing intrinsic nerves. Pinaverium bromide affec ted the slow wave by selectively inhibiting the plateau potential that is associated with generation of contractile activity. Pinaverium, si milar to diltiazem and D600, produced reductions in cholinergic respon ses as well as spontaneous contractions. The IC50 values for inhibitio n of cholinergic responses for pinaverium, diltiazem, and D600 were 1. 0 x 10(-6), 4.1 x 10(-7), and 5.3 x 10(-7) M, respectively. The IC50 v alues for inhibition of spontaneous contractile activity for pinaveriu m, diltiazem, and D600 were 3.8 x 10(-6), 9.7 x 10(-7), and 8.0 x 10(- 7) M, respectively. Increases in contractility by carbachol were aboli shed by pretreatment with either pinaverium or D600. In addition, neit her pinaverium nor D600 had any effects on the inhibitory NO-mediated relaxations. These data provide a rationale for the use of pinaverium in the treatment of colonic motor disorders where excessive contractio n has to be suppressed.