Assessment of the adrenergic effects of orphenadrine in rat vas deferens.
The peripheral adrenergic effects of orphenadrine, an antiparkinsonian drug, have been evaluated in the rat vas deferens to investigate whether these properties are the same as those of other phencyclidine ligands. In the low micromolar range, orphenadrine enhanced electrically-evoked and exogenous noradrenaline contractile responses in the epididymal portion of rat vas deferens. It also induced spontaneous activity that was inhibited by prazosin (1 microM) but not by atropine (20 nM). It inhibited accumulation of [3H]noradrenaline in rat vas deferens (IC50 = 14.2+/-2.3 microM). Orphenadrine competitively inhibited [3H]nisoxetine binding in rat vas deferens membranes (Ki = 1.05+/-0.20 microM). It can be concluded that orphenadrine, at low micromolar concentrations, interacts with the noradrenaline reuptake system inhibiting its functionality and thus potentiating the effect of noradrenaline.
Pubill
D
D
Laboratory of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Barcelona, Zona Univ. Pedralbes, Spain. pubill@farmacia.far.ub.es
Canudas
A M
AM
Pallàs
M
M
Sureda
F X
FX
Escubedo
E
E
Camins
A
A
Camarasa
J
J
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D004822:Epididymis / Q000187:drug effects; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D009966:Orphenadrine / Q000494:pharmacology*; D010622:Phencyclidine / Q000037:antagonists & inhibitors*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014649:Vas Deferens / Q000187:drug effects
D018663:Adrenergic Agents; D008024:Ligands; D018727:Muscarinic Antagonists; D005473:Fluoxetine; C011386:nisoxetine; D001285:Atropine; D009966:Orphenadrine; D010622:Phencyclidine; D009638:Norepinephrine; D011224:Prazosin