Drug profile of new benzofurane derivatives in guinea-pig isolated heart muscle preparations.
The recently synthesized benzofuranylethanolamines GE 68, GE 70, GE 76, RG 16 and RG 25, were studied in guinea-pig isolated papillary muscles and right atria. With regard to their inotropic, chronotropic and beta-adrenoceptor-blocking activity, these compounds were compared with the reference drug propafenone. GE 68, GE 70 and GE 76 were almost equally potent as propafenone in reducing the isometric force of contraction of papillary muscles, while RG 16 and RG 25 were less effective than the parent drug. GE 70 decreased the spontaneous rate of activity of right atria in a similar concentration range as propafenone, whereas GE 68 showed a more, and GE 76, RG 16 and RG 25 a less pronounced negative chronotropy. In contrast to the reference compound propafenone, the derivatives GE 70, GE 76 and RG 16 lacked any beta-adrenoceptor-blocking activity, while GE 68 and RG 25 exerted only a weak and nonsignificant effect. It is concluded that the formation of a benzofurane ring in the propafenone molecule did not cause a prominent change in negative inotropic and negative chronotropic effects, but resulted in a decrease or loss of beta-adrenoceptor-blocking activity. Additionally, an exchange of the phenylethyl group (GE 68, GE 70, GE 76) on the benzofurane ring by a methyl (RG 25) or ethyl group (RG 16), attenuated the negative inotropic and chronotropic potency.
Lemmens Gruber
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Institute of Pharmacology and Toxicology, University of Vienna, Pharmazie-Zentrum, Vienna, Austria.
Studenik
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Marei
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Heistracher
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009921:Metaproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D011405:Propafenone / Q000494:pharmacology; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D001572:Benzofurans; C088995:GE 68; D009921:Metaproterenol; D011405:Propafenone