A possible mechanism on the potentiating vascular effect of coadministration of ifenprodil tartrate and calcium hopantenate: a study in the internal carotid artery.
Recently, it has been proposed that the combined administration of ifenprodil tartrate and calcium hopantenate might produce a beneficial synergistic effect in the treatment of cerebrovascular diseases. To further examine this clinical phenomena, the blood flow in the internal carotid arteries of the rat and the isometric tension of canine internal carotid arteries were measured with a transit-time ultrasonic volume flowmeter and a force transducer, respectively. Ifenprodil tartrate produced a sustained increase in the internal carotid arterial blood flow of rats, while calcium hopantenate had no effect. However, the increase in the internal carotid arterial blood flow induced by ifenprodil tartrate was significantly enhanced by calcium hopantenate. Ifenprodil tartrate caused a dose-related relaxation of K+-induced contractions in the isolated canine internal carotid arteries, while calcium hopantenate had no effect. The dose-response curve of ifenprodil tartrate was shifted to the left by pre-incubation in calcium hopantenate. Ifenprodil tartrate inhibited the K+-induced Ca2+ uptake in the canine internal carotid arteries, and the inhibition induced by ifenprodil tartrate was significantly enhanced by calcium hopantenate. These results suggest that the observed enhancement by calcium hopantenate of the ifenprodil tartrate effect on the internal carotid arterial blood flow was due to increased vascular myorelaxation resulting from the influence of calcium hopantenate on the Ca2+ movement.
Shibuya
T
T
Department of Pharmacology, Tokyo Medical College, Japan.
Honda
H
H
Watanabe
Y
Y
Shimura
H
H
Matsuda
H
H
Tsuji
H
H
Izumisawa
M
M
Iwata
T
T
Irino
O
O
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002343:Carotid Artery, Internal / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000188:drug therapy; D004285:Dogs; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010205:Pantothenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D010880:Piperidines; C016030:pantogab; D010205:Pantothenic Acid; D005680:gamma-Aminobutyric Acid; C010739:ifenprodil; D002118:Calcium