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In vitro effects of calcium entry blockers, chlorpromazine and fenoterol upon human pregnant myometrium contractility
Author(s) -
Ballejo Gustavo,
Calixto João B.,
Medeiros Yara S.
Publication year - 1986
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.1476-5381.1986.tb11151.x
Subject(s) - verapamil , cinnarizine , nifedipine , chemistry , calcium , pharmacology , chlorpromazine , endocrinology , medicine , organic chemistry
1 The inhibitory effects of nifedipine, verapamil, cinnarizine (calcium entry blockers), chlorpromazine (a putative calmodulin antagonist) and fenoterol (a β 2 ‐adrenoceptor agonist) on contractility in human isolated pregnant myometrium were studied. 2 Spontaneous contractions (present in 93% of the preparations) were inhibited in a concentration‐related manner by these compounds in the following order of potency: nifedipine > verapamil >> cinnarizine > chlorpromazine. Cinnarizine was effective only at a concentration greater than 100 μM. Fenoterol, at 10 μM, did not produce an inhibitory effect but decreased the frequency of spontaneous contractions. 3 All drugs, except fenoterol, produced a concentration‐dependent relaxation of K + ‐induced contractions in the following order of sensitivity: nifedipine > verapamil >> chlorpromazine. Cinnarizine produced only about 40% of relaxation. Under these conditions nifedipine and verapamil were about 80 and 5 fold more potent respectively than when tested against spontaneous contractions. The potencies of chlorpromazine and cinnarizine did not differ in the two experimental conditions. 4 Both the spontaneous and K + ‐induced contractions were inhibited in a time‐dependent manner in Ca 2+ ‐free media and the responses were almost completely abolished in 70–100 min. Calcium addition to the medium rapidly restored both spontaneous or K + ‐induced contractions. 5 To investigate further the role of intracellular calcium, K + ‐depolarized preparations contracted by calcium 3 mM (40–60% of maximal contractions) were relaxed by these compounds. Nifedipine and verapamil showed a relaxation time course similar to that induced by calcium removal. Cinnarizine and fenoterol had no relaxant effect while chlorpromazine induced a slight and slow relaxation. 6 These findings suggest that calcium influx and calmodulin are involved in spontaneous contractions of pregnant human myometrium in vitro. Since nifedipine and verapamil were more potent against K + ‐induced than spontaneous contractions, calcium channels activated by these conditions could be different. Finally, fenoterol, a β 2 ‐adrenoceptor agonist, widely used as a tocolytic agent, blocked neither spontaneous nor K + ‐induced contractions.