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KMID : 0370219880320020101
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Yakhak Hoeji
1988 Volume.32 No. 2 p.101 ~ p.111
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Interaction of Antihistaminics with Muscarinic Receptor(Ⅰ)
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Abstract
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[^(c)H] Quinuclidinyl 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 37°C for formation and dissociation of the QNB receptor complex were 0.38 x 109 M-1 min-1 and 1.6 x 10-2 min-1, respectively. The mean value for the dissociation constant from the pairs of the rate constants was 43. 2 pM and this value was similar to the value(44.8pM) determined from Scatchard analysis. CHP decreased association rate constant, indicating increase in Kn value. Decrease in affinity without affecting the binding site concentration(Bma:) for C3H)QNB binding by CHP was also demonstrated by Scatchard analysis. K1 values for H1-blockers that inhibited specific C3H)QNB binding were 0.02´-´4.8pM. Cirnetidine with K; value of 230pM, however, was ineffective in displacing C3HJQNB binding at concentration of 50μM. 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 receptor and anticholinergic side effects of these drugs are mainly due to this receptor blocking mechanism.
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KEYWORD
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