항 Histamine제와 Muscarinic Recepter와의 상호작용(I) 심장 muscarinic recepter에 대한 작용

• 영문명: Interaction of Antihistaminics with Muscarinic Receptor(I) Action on the cardiac muscarinic receptor
• 발행기관: 대한약학회
• 저자명: 이신웅(Shin Woong Lee) 박영주(Yeung Joo Park) 이정수(Jeong Soo Lee) 하광원(Kwang Wan Ha) 진갑덕(Kap Duck Jin)
• 간행물 정보: 『약학회지』제32권 제2호 (1988년), 101~111쪽, 전체 11쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1988.04.29

영문 초록

[3H] Quinuelidinyl benzilate(QNB) binding assays were performed in the dog ventricular sarcolemma fraction enriched approx. 32-fold in sarcolemma compared to the starting homogenate to elucidate the effect of antihistaminics on cardiac muscarinic receptor. Chlorpheniramine(CHP) inhibited specific binding of [3H]QNB and delayed the equilibrium binding. The rate constants at 37oC for formation and dissociation of the QNB receptor complex were 0.38 X 1O9M-1min-1 and 1.6 X 1O-2min-1, respectively. The mean value for the dissociation constant from the pairs of the rate constants was 43.2pM and this value was similar to the value(44.8pM) determined from Scatchard analysis. CHP decreased association rate constant, indicating increase in KD value. Decrease in affinity without affecting the binding site concentration(Bmax) for [3H]QNB binding by CHP was also demonstrated by Scatchard analysis. Ki values for H1-blockers that inhibited specific [3H]QNB binding were 0.02-4.8mcM. Cimetidine with Ki value of 230mcM, however, was ineffective in displacing [3H]QNB binding at concentration of 50mcM. The Hill coefficient for H1-blockers were about one. The results indicate that H1-antihistaminics inhibit [3H]QNB binding by interaction with myocardiac muscarinic cholinergic recepter and anticholinergic side effects of these drugs are mainly due to this recepter blocking mechanism.