{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T20:45:54Z","timestamp":1764276354084},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3226,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>To investigate the effects of various chemical classes of antipsychotic drugs: haloperidol, thioridazine, pimozide and clozapine, on the G\u2010protein\u2010activated inwardly rectifying K<jats:sup>+<\/jats:sup> (GIRK) channels, we carried out <jats:italic>Xenopus<\/jats:italic> oocyte functional assays with GIRK1 and GIRK2 mRNAs or GIRK1 and GIRK4 mRNAs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In oocytes co\u2010injected with GIRK1 and GIRK2 mRNAs, application of each of the various antipsychotic drugs immediately caused a reduction of inward currents through the basally active GIRK channels. These responses were not observed in the presence of 3\u2003m<jats:sc>M<\/jats:sc> Ba<jats:sup>2+<\/jats:sup>, which blocks the GIRK channels. In addition, in uninjected oocytes, none of the drugs tested produced any significant current response. These results indicate that all the antipsychotic drugs tested inhibited the brain\u2010type GIRK1\/2 heteromultimeric channels. Furthermore, similar results were obtained in oocytes co\u2010injected with GIRK1 and GIRK4 mRNAs, indicating that the antipsychotic drugs also inhibited the cardiac\u2010type GIRK1\/4 heteromultimeric channels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>All the drugs tested inhibited, in a concentration\u2010dependent manner, both types of GIRK channels with varying degrees of potency and effectiveness at micromolar concentrations. Only pimozide caused slight inhibition of these channels at nanomolar concentrations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that the various antipsychotic drugs acted as inhibitors at the brain\u2010type and cardiac\u2010type GIRK channels. Our results suggest that inhibition of both types of GIRK channels by these drugs underlies some of the side effects, in particular seizures and sinus tachycardia, observed in clinical practice.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>129<\/jats:bold>, 1716\u20131722; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703224\">10.1038\/sj.bjp.0703224<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703224","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:38:28Z","timestamp":1106944708000},"page":"1716-1722","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Inhibition by various antipsychotic drugs of the G\u2010protein\u2010activated inwardly rectifying K<sup>+<\/sup> (GIRK) channels expressed in <i>Xenopus<\/i> oocytes"],"prefix":"10.1111","volume":"129","author":[{"given":"Toru","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutaka","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiro","family":"Kumanishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"807","article-title":"Haloperidol: twenty years' clinical experience","volume":"39","author":"AYD F.J.","year":"1978","journal-title":"J. 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