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Stereoselective effects of the enantiomers, quinidine and quinine, on depolarization‐ and agonist‐mediated responses in rat isolated aorta
Author(s) -
Pozo Buensuceso Férnandez,
PérezVizcaíno Francisco,
Villamor Eduardo,
Zaragozá Francisco,
Tamargo Juan
Publication year - 1996
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.1476-5381.1996.tb15161.x
Subject(s) - quinidine , quinine , depolarization , chemistry , agonist , pharmacology , medicine , biochemistry , receptor , malaria , immunology
1 The effects of the two enantiomers, quinidine and quinine, were studied on depolarization‐ and agonist‐induced isometric contractions in rat isolated thoracic aortic rings. 2 Quinidine or quinine (10 −6 m − 3 × 10 −4 m ) produced a concentration‐dependent relaxation of 80 mM KCl‐contracted rings, the pD 2 values being 4.89 and 4.23, respectively. Thus, quinidine was about 4 − 5 times more potent than quinine. 3 The voltage‐dependence of quinidine‐ and quinine‐induced inhibition was studied in rings that had been incubated in 5 or 40 mM KCl Ca 2+ ‐free solution and then contracted by changing the bath solution to 100 mM KCl and 2 mM Ca 2+ . The inhibitory effects of quinidine were significantly enhanced when the rings were preincubated in 40 mM KCl (depolarizing conditions), when compared to normally polarized rings. In contrast, the effects of quinine were similar in 5 or 40 mM KCl solution. 4 The antagonism of noradrenaline (NA)‐induced contractions by low concentrations of quinidine (< 10 −4 m ) and quinine (> 3 × 10 −4 m ) was competitive, as demonstrated by the concentration‐dependent parallel rightward shift of the NA concentration‐response curves (pA 2 values 6.20 and 5.68, respectively, P > 0.05). 5 At low concentrations (≤ 3 × 10 −5 m ), quinidine and quinine did not shift the concentration‐response curve to 5‐hydroxytryptamine (5‐HT) or endothelin‐1, whereas at higher concentrations they produced a downward shift of these curves. Quinidine and quinine (> 10 −4 m ) inhibited to a similar extent both the phasic (induced in Ca 2+ ‐free media) and tonic responses (after restoring extracellular Ca 2+ ) induced by 5‐HT. 6 In conclusion, quinidine and quinine produced a stereoselective inhibition of depolarization and NA‐induced contractions, quinidine being more potent than quinine. The inhibition of KCl‐induced contractions could be attributed to inhibition of Ca 2+ entry. Both drugs also behaved as competitive antagonists of α 1D ‐adrenoceptors. At high concentrations, quinidine and quinine also decreased the contractions induced by endothelin‐1 and 5‐HT in a non‐stereoselective manner.