Inhibitory Effects of Psychotropic Drugs on the Acetylcholine Receptor-Operated Potassium Current (I<sub>K.ACh</sub>) in Guinea-Pig Atrial Myocytes

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  • OKADA Muneyoshi
    Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
  • WATANABE Shinya
    Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
  • MATADA Takashi
    Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
  • ASAO Yoko
    Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
  • HAMATANI Ramu
    Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
  • YAMAWAKI Hideyuki
    Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
  • HARA Yukio
    Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan

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  • Inhibitory Effects of Psychotropic Drugs on the Acetylcholine Receptor-Operated Potassium Current (I[K.ACh]) in Guinea-Pig Atrial Myocytes

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Abstract

Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5’-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

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