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VASORELAXANT ACTION OF CAROVERINE FUMARATE (A QUINOXALINE DERIVATIVE), A CALCIUM‐BLOCKING AGENT
Author(s) -
ISHIDA YUKISATO,
OZAKI HIROSHI,
SHIBATA SHOJI
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb10945.x
Subject(s) - verapamil , contraction (grammar) , calcium , chemistry , aorta , vascular smooth muscle , biophysics , stereochemistry , endocrinology , medicine , smooth muscle , biology , organic chemistry
1 Caroverine fumarate, 1‐(2‐diethylaminoethyl)‐ 3 ‐( p ‐methoxy‐benzyl)‐1,2‐dihydro‐2‐quinoxalinone fumarate, caused a greater inhibition of the pressor response to KCl (8 × 10 −2 m ) than that to noradrenaline (10 −6 m ) in the rat hindquarter preparation. 2 In the isolated aorta of the rat, caroverine (up to 10 −6 m ) markedly suppressed the contraction caused by KCl (4 × 10 −2 m ) (high‐K) but had little effect on the contractile response to noradrenaline (10 −6 m ) whether added before the spasmogen or in its presence. 3 In the high‐K‐treated aorta, caroverine shifted the concentration‐response curve for external calcium to the right, competitively. The negative logarithm of the affinity (pA 2 ) of caroverine was calculated to be approx. 7. 4 Increased 45 Ca uptake of the high‐K‐treated aorta measured by a modified lanthanum method was inhibited by either caroverine (3 × 10 −6 m ) or verapamil (10 −6 m ). 5 Concentrations of caroverine and verapamil reducing high‐K‐induced aortic contraction to 50% of its maximum were 2.4 × 10 −7 and 6.6 × 10 −8 m respectively. 6 Following washout the caroverine‐induced inhibition of high‐K‐induced aortic contraction was more rapidly restored than the verapamil‐induced inhibition. 7 These results suggest that caroverine fumarate is a specific and readily reversible calcium influx inhibitor in the rat vascular smooth muscle.