Vasorelaxant and negative inotropic effects of gallopamil and LU49700, a metabolite of gallopamil, on isolated rat aorta and guinea-pig ventricular myocardium.
The effects of LU49700 (CAS 116759-60-5), the main metabolite of gallopamil (CAS 16662-47-8) on the mechanical response of isolated rat aortic and guinea-pig ventricular papillary muscle preparations were compared with those of gallopamil. Gallopamil and LU49700 inhibited the 64 mmol/l KCl-induced contraction of rat aorta in a concentration-dependent manner. The vasorelaxant potency of LU49700 was 244 times weaker than that of gallopamil. Gallopamil and LU49700 produced concentration-dependent negative inotropic effects on isolated right ventricular papillary muscles. The negative inotropic potency of LU49700 was 418 times weaker than that of gallopamil. These findings indicate that LU49700 has a weaker cardiovascular depressant potency than gallopamil. Therefore, LU49700 may not mediate the effects of gallopamil for treating subjects with cardiovascular diseases.
Noguchi
K
K
Pharmacology Laboratory, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Takahashi
K
K
Kaneko
K
K
Higuchi
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003864:Depression, Chemical; D005711:Gallopamil / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006586:Hexanes / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D006586:Hexanes; C111592:LU 49700; D005711:Gallopamil