Pinaverium acts as L-type calcium channel blocker on smooth muscle of colon.
The effect of pinaverium was electrophysiologically characterized and compared with the established L-type calcium channel blockers diltiazem, D600, and nitrendipine on canine colonic circular smooth muscle. Effects were studied on the electrical activity of the smooth muscle cells, in particular the spontaneously occurring slow wave. In addition, effects were examined on spontaneous contraction patterns and contractile activities generated by stimulation of cholinergic nerves or directly by stimulating muscarinic receptors. Effects were also examined on excitation of NO-releasing intrinsic nerves. Pinaverium bromide affected the slow wave by selectively inhibiting the plateau potential that is associated with generation of contractile activity. Pinaverium, similar to diltiazem and D600, produced reductions in cholinergic responses as well as spontaneous contractions. The IC50 values for inhibition 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 values for inhibition of spontaneous contractile activity for pinaverium, 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 abolished by pretreatment with either pinaverium or D600. In addition, neither 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 contraction has to be suppressed.
Malysz
J
J
Intestinal Disease Research Programme, McMaster University, Hamilton, ON, Canada.
Farraway
L A
LA
Christen
M O
MO
Huizinga
J D
JD
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D003109:Colonic Diseases, Functional / Q000188:drug therapy; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D009025:Morpholines; D018721:Muscarinic Agonists; D002217:Carbachol; C013199:pinaverium