title: Celiprolol, a potent cardioselective beta 1-adrenoceptor antagonist with mild alpha 2-adrenoceptor antagonist properties.
abstract: Celiprolol is a cardioselective beta-adrenoceptor antagonist, with interesting propranolol-insensitive cardiostimulatory, vasodilatory and bronchodilatory effects. Recent reports suggest that mild alpha 2-adrenoceptor antagonism may contribute to these effects. The present investigation further explored the alpha 2 effects of celiprolol. In isolated electrically-stimulated rat atria celiprolol (1.0 and 10 mumol/l) significantly increased the release of [3H]-norepinephrine, consistent with the blockade of pre-junctional alpha 2-adrenoceptors. Evidence for post-synaptic alpha 2-adrenoceptor antagonist activity was obtained in studies of the effects of celiprolol on the pressor response to clonidine and either phenylephrine or methoxamine in perfused hind-limbs of dogs (pretreated with mecamylamine and propranolol) and pithed rats. In the dog, celiprolol (10 mg/kg) significantly inhibited the vasoconstrictor response of clonidine while in the rat higher doses were required (> or = 12.5 mg/kg). Celiprolol did not affect the pressor response induced by alpha 1-agonists. We conclude that celiprolol possesses a mild alpha 2-adrenoceptor blocking action which may contribute to its unconventional profile.
authors.affiliation: Department of Pharmacology, Revlon Health Care, Research and Development Division, Tuckahoe, New York 10707.
authors.forename: P S
authors.initials: PS
authors.lastname: Wolf
authors.forename: T P
authors.initials: TP
authors.lastname: Pruss
authors.forename: M J
authors.initials: MJ
authors.lastname: Rand
authors.forename: R D
authors.initials: RD
authors.lastname: Smith
authors.forename: W S
authors.initials: WS
authors.lastname: Mann
authors.forename: D V
authors.initials: DV
authors.lastname: Romano
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017272:Celiprolol / Q000494:pharmacology*; D004285:Dogs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D051381:Rats
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D017272:Celiprolol