Cerebral vasodilating and spasmolytic actions of a new Ca-antagonist, clentiazem (TA-3090), in anesthetized animals.
The effect of a new 1,5-benzothiazepine calcium antagonist, clentiazem (TA-3090), on the cerebral circulation was studied in anesthetized animals. Intravenous infusion of clentiazem at doses of 2.5, 5, and 10 micrograms/kg/min increased vertebral blood flow without causing hypotension in anesthetized dogs. After i.v. injection to anesthetized dogs, clentiazem, diltiazem, and papaverine all dose-dependently increased the regional cerebral blood flow and raised the intracranial pressure (ICP). However, the effect of clentiazem on the ICP was weaker than that of diltiazem and papaverine. In anesthetized monkeys, clentiazem (3-100 micrograms/kg, i.v.) increased the internal carotid blood flow to the intracranial tissues. In anesthetized cats, topical or i.v. clentiazem inhibited basilar artery vasospasm induced by the topical application of serotonin, prostaglandin F2 alpha, and incubated blood. These findings suggest that clentiazem has favorable properties as a cerebral vasodilator.
Murata
S
S
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Kikkawa
K
K
Nagao
T
T
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004110:Diltiazem / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007427:Intracranial Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D014665:Vasodilator Agents; D012701:Serotonin; C056595:clentiazem; D015237:Dinoprost; D010208:Papaverine; D004110:Diltiazem