SK&F 104078, a post-junctionally selective alpha 2-adrenoceptor antagonist in the human saphenous vein in vitro.
The present study investigated the effects of SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxy]-3-methyl-1H,2,3,4,- tetrahydro-3-benzazapine) at pre- and post-junctional alpha 2-adrenoceptors in the human isolated saphenous vein. Noradrenaline (0.001-100 mumol/l) produced concentration-dependent contractions of the human saphenous vein which were competitively antagonised by the alpha 1-adrenoceptor antagonist prazosin (0.01-1.0 mumol/l) and the alpha 2-adrenoceptor antagonist, rauwolscine (0.01-1.0 mumol/l), indicating the presence of both post-junctional alpha 1- and alpha 2-adrenoceptors in this preparation. The selective alpha 2-adrenoceptor agonist, UK-14,304 (0.01-100 mumol/l) also produced concentration-dependent contractions of the human saphenous vein which were antagonised by both rauwolscine (0.1 mumol/l) and prazosin (0.1 mumol/l). In the presence of angiotensin II (0.05 mumol/l), which itself produced a transient contraction, rauwolscine (0.1 mumol/l) produced a rightward shift of the UK-14,304 concentration-response curve while prazosin (0.1 mumol/l) had no effect. SK&F 104078 (10.0 mumol/l) under these conditions also produced a rightward shift of the concentration-response curve to UK-14,304, but was at least 100-fold less potent than rauwolscine. At pre-junctional alpha 2-adrenoceptors, exogenous noradrenaline (0.01 and 0.1 mumol/l) induced a concentration-dependent inhibition of stimulation-evoked [7-3H]-noradrenaline release from the human saphenous vein in vitro, which was antagonised by rauwolscine (0.1 mumol/l) and tolazoline (10.0 mumol/l) but not by SK&F 104078 (10.0 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
Beecham Pharmaceuticals Research Division, Epsom, Surrey, UK.
S P
SP
Roberts
J
J
Kelly
M A
MA
Cawthorne
M V
MV
Sennitt
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000494:pharmacology*; D000068438:Brimonidine Tartrate; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000187:drug effects / Q000648:ultrastructure; D009638:Norepinephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects* / Q000648:ultrastructure
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D011810:Quinoxalines; C054935:SK&F 104078; D000068438:Brimonidine Tartrate; D009638:Norepinephrine