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- W97910510 abstract "The effects of tiemonium on various membrane events preceding smooth muscle fibre contraction, have been studied in vitro. Classical molecular pharmacological models and methods were used: stimulation of muscarinic, histamine H1 and alpha-adrenergic receptors; induction of contraction by release of membrane phospholipid bound Ca2+ ions, or by intracytoplasmic influx of this cation in depolarized preparations. At each level of investigation, tiemonium was studied comparatively with two reference antispasmodics, atropine and papaverine. Like atropine, tiemonium competitively antagonizes cholinergic stimulation. It also interferes with the contracting effects of BaCl2, as does papaverine. In contrast to papverine, however, tiemonium shows an affinity for histamine H1-receptors, and does not affect alpha-adrenergic receptor stimulation. Tiemonium is therefore a novel antispasmodic which blocks the cholinergic receptor, but being less specific than atropine. This non-specific facet makes it almost as polyvalent as papaverine, in its general inhibition of spasmogenic substances, but its mechanism of action is very different. Whereas papaverine slows intracytoplasmic Ca2+ influx, tiemonium inhibits release, and thus availability, of the same ion. Tiemonium has a totally different mechanism of antispasmodic action from that other substances in the same pharmacological class. The marked competitive interference with acetylcholine and the very weak competitive antagonism of histamine are completed by a membrane stabilizing action. In particular, the latter reinforces the binding of calcium to membrane phospholipids. The absence of any interaction of tiemonium with noradrenaline is compatible with recent theories for noradrenaline's action, which evoke calcium exchanges in an intracytoplasmic compartment. Finally, the results raise the question of the pharmacological suitability of the term papaverine-like for describing non-specific antispasmodics." @default.
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- W97910510 date "1976-10-01" @default.
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- W97910510 title "Different membrane mechanisms of action for tiemonium; a comparison with atropine and papaverine." @default.
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