Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The properties of the newly developed selective beta 1-adrenoceptor antagonist bisoprolol (EMD 33152) were investigated by in vitro and in vivo studies. Binding studies with (-)-[125I] iodocyanopindolol (ICYP) revealed that the affinity of (+/-)-bisoprolol to beta 1-adrenoceptors was approximately 100 times higher than to beta 2-adrenoceptors. This high beta 1-adrenoceptor selectivity of bisoprolol could be confirmed in binding studies with the tritiated compound (-)[3H] bisoprolol, which labelled in rabbit lung membranes--a tissue known to contain 80% beta 1- and 20% beta 2-adrenoceptors--exclusively beta 1-adrenoceptors. In physiological studies, (+/-)-bisoprolol was found to be devoid of any intrinsic sympathomimetic activity (ISA), since it had no positive chronotropic effects on spontaneously beating right atria of reserpinized rats. On isolated electrically driven human right atria, (+/-)-bisoprolol was approximately 30 times more potent in antagonizing the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline (pA2-value, 8.42) than the beta 2-adrenoceptor-mediated positive inotropic effect of procaterol (pA2-value, 6.99). To test the beta 1-adrenoceptor selectivity in vivo, the effects of bisoprolol administration (1 X 10 mg/day for 9 days) on lymphocyte beta 2-adrenoceptor density [assessed by (-)-ICYP binding] in healthy volunteers were compared with those of the nonselective beta-adrenoceptor antagonists propranolol (4 X 40 mg/day for 9 days) without ISA, and pindolol (2 X 5 mg/day for 9 days) with ISA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bisoprolol (EMD 33512), a highly selective beta 1-adrenoceptor antagonist: in vitro and in vivo studies. 243 95

The pharmacodynamic activity of (+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol- hemifumarate (bisoprolol, EMD 33 512) has been investigated under in vitro and in vivo conditions. Bisoprolol was found to be an effective beta-adrenoceptor antagonist, the pA2 values determined against isoprenaline in guinea pig atria and tracheal muscle being 7.45 and 6.41, respectively. Thus, the selectivity ratio of bisoprolol in favour of beta 1-adrenoceptors is 11. Inhibition of the isoprenaline-induced tachycardia in guinea pigs indicated a long duration of action for bisoprolol. The compound was devoid of intrinsic sympathomimetic activity as shown by the lack of effect on heart rate in anaesthetized and reserpine pretreated rats. Studies in rabbits and guinea pigs revealed a local anaesthetic activity of bisoprolol at high concentrations. Bisoprolol protected the hearts of anaesthetized dogs against the sequelae of intermittent coronary occlusions, as judged by the reduction of the ST-segment elevation in the epicardial ECG. Bisoprolol exerted a blood pressure lowering effect in conscious renal hypertensive dogs after oral administration of 30 micrograms/kg. There was no indication of any action on the CNS in monkeys following an oral dose of up to 8 mg/kg.
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PMID:Pharmacodynamic profile of the selective beta 1-adrenoceptor antagonist bisoprolol. 287 Jul 20