Cyclandelate as a calcium modulating agent in rat cerebral cortex.
Cyclandelate is clinically effective in a variety of cerebrovascular indications, but its precise mode of action is unclear. Hence, this study investigated the interaction of cyclandelate, cyclandelate alcohol and cyclandelate acid with the binding sites for radioactively labelled 3H-nitrendipine, a Ca++ entry blocker of the 1,4-dihydropyridine type, on rat cerebral cortex membranes. Cyclandelate showed a dissociation constant (Kd) of 7.1 +/- 1.4 X 10(-5) mol/L (35% inhibition of 3H-nitrendipine binding at 2 X 10(-4) mol/L cyclandelate), cyclandelate alcohol had a Kd value of 1.7 +/- 0.1 X 10(-4) mol/L (maximal 70% inhibition of 3H-nitrendipine binding) whereas cyclandelate acid was inactive. For comparison, nifedipine (Kd of 2.6 +/- 0.3 X 10(-9) mol/L inhibition of 68% of 3H-nitrendipine binding), d-cis diltiazem (Kd of 1.1 +/- 0.1 X 10(-7) mol/L enhancement of 39% of 3H nitrendipine binding) and +/- -verapamil [Kd values of 1.4 +/- 0.4 X 10(-7) mol/L (38% inhibition) and 5.3 +/- 1.7 X 10(-4) mol/L (62% inhibition)] were used. Thus, cyclandelate may exert its clinical activity in cerebral ischaemia or hypoxia at least in part through a calcium modulatory effect.
D000818:Animals; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003495:Cyclandelate / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology*; D009568:Nitrendipine; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008333:Mandelic Acids; D011978:Receptors, Nicotinic; D003495:Cyclandelate; D009568:Nitrendipine