Reference

Hemodynamic characterization of a new b-receptor blocker celiprolol (ST 1396) at rest and during ergometer exercise compared with propranolol (Inderal)

Hemodynamic characterization of a new b-receptor blocker celiprolol (ST 1396) at rest and during ergometer exercise compared with propranolol (Inderal). Bonelli, J.; Magometschnigg, D.; Hitzenberger, G.; Kaik, G. (Abt. Klin. Pharmakol., I. Med. Universitaetsklin. Wien, Vienna, Austria). Wien. Klin. Wochenschr., 90(10), 350-4 (German) 1978. CODEN: WKWOAO. ISSN: 0043-5325. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) In resting subjects, the cardioselective b-blocker celiprolol (I) [57470-78-7] (15 mg i.v.) increased the heart rate and heart minute vol., probably owing to some intrinsic sympathomimetic activity of I. The stroke vol. increased during exercise after I treatment compared to control trials, whereas the heart rate showed a smaller increase than in control trials during light exercise and was lower than in control trials during intense exercise. Evidently I blocks the cardiac receptors mediating the pos. chronotropic effect of catecholamines, but not the receptors mediating the pos. inotropic effect. These results contrasted markedly with those obtained with propranolol, a non-cardioselective b-blocker.

Effects of celiprolol (REV 5320), a new cardioselective beta-adrenoceptor antagonist, on in vitro adenylate cyclase, alpha- and beta-adrenergic receptor binding and lipolysis

Effects of celiprolol (REV 5320), a new cardioselective beta-adrenoceptor antagonist, on in vitro adenylate cyclase, alpha- and beta-adrenergic receptor binding and lipolysis. Van Inwegen, R. G.; Khandwala, A.; Weinryb, I.; Pruss, T. P.; Neiss, E.; Sutherland, C. A. (Res. Dev. Div., Revlon Health Care Group, Tuckahoe, NY 10707, USA). Arch. Int. Pharmacodyn. Ther., 272(1), 40-55 (English) 1984. CODEN: AIPTAK. ISSN: 0003-9780. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 Against the stimulation of adenylate cyclase [9012-42-4] from dog ventricular muscle by isoproterenol [7683-59-2], REV 5320 (I) [57470-78-7] had a Ki of 2.6 ′ 10-7M which was about 1/20 the potency of propranolol. At 100 mM, I did not affect histamine or dopamine concn.-response curves for the stimulation of adenylate cyclase from guinea pig cerebral cortex. By itself, I (￡1 mM) did not affect basal adenylate cyclase activity from either prepn. With in vitro radioligand binding assays to directly measure b-adrenergic receptor interactions, I had Ki values of 1.4 ′ 10-7-8.3 ′ 10-6M. A 35-fold b1-selectivity was noted with membranes from rat heart vs. rat reticulocytes, which supports previously reported in vivo data on cardioselectivity. No difference in affinity to b-receptors was noted with frog vs. turkey erythrocyte membranes which supports the contention that these 2 nonmammalian systems are not predictive of b1-/b2-specificity with mammalian systems. I also showed some selective a2-adrenoceptor antagonism against [3H]yohimbine binding vs. [3H]prazosin binding to membranes from rat cerebral cortex. With rat adipocytes, <300 mM I did not stimulate basal lipolysis in the presence or absence of 10 mM IBMX. I inhibited isoproterenol-induced lipolysis with a potency ~2 times greater than practolol. Unlike propranolol, I at very high concns. did not show nonspecific inhibition of lipolysis induced with cyclic nucleotides. These and other published data suggest that (1) in vitro b-adrenergic receptor antagonist activity can be demonstrated for I, (2) cardioselectivity is due to a combination of many factors including stereochem. of the mol. and in vivo distribution and metab., (3) I does not possess nonspecific membrane activity, (4) the intrinsic sympathomimetic activity of I is selectively obsd. in some but not all in vitro test models, (5) I has about a 10-fold selectivity for a2- vs. a1-receptors which is relatively unique to b-antagonists.