[Pharmacological studies of celiprolol: II. Alpha 2-Adrenoceptor blocking effects of a cardioselective beta-blocker, celiprolol].
alpha-Adrenoceptor blocking effects of the cardioselective beta-blocker celiprolol were tested. 1. Celiprolol antagonized the contractions induced by UK-14304, but not those by phenylephrine, in isolated rat tail arteries with a pA2 value of 4.95. 2. In the isolated rat vas deferens, twitch contractions elicited by the transmural electrical stimulation (TS) were almost blocked by TTX (10(-7) M). Clonidine inhibited the TTX-sensitive contraction in a concentration-dependent manner. Celiprolol produced little effect on the inhibitory effects of clonidine. The concentration-inhibition curve of clonidine was shifted to the right by yohimbine (10(-8) M), but not by prazosin (10(-8) M). 3. Although celiprolol slightly increased the 3H-efflux to TS from the [3H]-norepinephrine-loaded rat vas deferens, the increment was not significant. Yohimbine (10(-7) M) significantly increased the 3H-efflux. TTX (10(-7) M) and bretylium (3 x 10(-5) M) blocked the 3H-efflux. 4. In the spinal rat treated with propranolol (3 mg/kg, i.v.) and prazosin (0.1 mg/kg, i.v.), celiprolol (30 and 100 mg/kg, i.v.) and yohimbine (0.1-1 mg/kg, i.v.) inhibited the pressor response to clonidine. 5. These results indicate that celiprolol may have a weak alpha 2-blocking effect which was more effective on postsynaptic alpha 2-receptors than presynaptic ones.
Miura
A
A
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Ukai
Y
Y
Matsuzaki
T
T
Ishima
T
T
Hayashi
S
S
Kano
S
S
Kimura
K
K
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D017272:Celiprolol; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011810:Quinoxalines / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013623:Tail / Q000098:blood supply; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011810:Quinoxalines; D015016:Yohimbine; D013779:Tetrodotoxin; D000068438:Brimonidine Tartrate; D017272:Celiprolol