title: Evidence that SK & F 104078 does not differentiate between pre- and postjunctional alpha 2-adrenoceptors.
abstract: We have investigated the proposed postjunctional selectivity of the alpha 2-adrenoceptor antagonist SK & F 104078 employing the pithed rat, rat isolated atrium and human saphenous vein preparations. In the pithed rat, SK & F 104078 (5 mg kg-1) produced a 20-fold shift in the prejunctional ID50 (concentration of agonist producing 50% inhibition of the cardioacceleration to a single stimulus) and a 3-fold shift in the postjunctional ED50 (concentration producing 50% of maximum rise in diastolic blood pressure) of the alpha 2-adrenoceptor agonist xylazine. However, the alpha 2-adrenoceptor antagonist yohimbine also showed apparent selectivity for prejunctional receptors in the pitched rat. In the rat isolated atrium, yohimbine was approximately 10 times more potent than SK & F 104078 at enhancing the stimulation-evoked release of tritium in tissues preincubated with (3H)-noradrenaline. In the human saphenous vein, yohimbine and SK & F 104078 had pA2 values of 7.40 and 6.33, respectively, against contractions to noradrenaline, so that yohimbine was again approximately ten times more potent than SK & F 104078. In conclusion, SK & F 104078 behaved like yohimbine in its relative potencies at pre- and postjunctional alpha 2-adrenoceptors both in vivo and in vitro, so that we fail to find any selectivity of SK & F 104078 for postjunctional alpha 2-adrenoceptors.
authors.affiliation: Department of Clinical Pharmacology, Royal College of Surgeons, Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Connaughton
authors.forename: J R
authors.initials: JR
authors.lastname: Docherty
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001552:Benzazepines / Q000494:pharmacology*; D003655:Decerebrate State; D006321:Heart / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects; D014991:Xylazine / Q000037:antagonists & inhibitors
chemical_list: D000317:Adrenergic alpha-Antagonists; D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D011942:Receptors, Adrenergic, alpha; C054935:SK&F 104078; D014991:Xylazine