Effects of desipramine on stimulation-induced contractions of the vas deferens of rats pretreated either chronically with desipramine or acutely with idazoxan.
In the present studies the effects of desipramine on the functional sensitivity of the prejunctional alpha 2-adrenoceptors of the vas deferens were studied in pithed rats; contractions of the tissue were evoked by electrical stimulation (6 Hz) of the spinal sympathetic outflow. Twenty-four hours after a single dose of desipramine (10 mg/kg, intraperitoneally) the inhibitory dose-response curves to either UK 14 304 or desipramine itself did not differ significantly from those seen in control animals, whereas both were displaced significantly to the right after 15 days pretreatment with desipramine. Thus the functional responsiveness of the prejunctional alpha 2-adrenoceptors of the vas deferens was reduced by chronic but not acute pretreatment with desipramine. In acute studies desipramine (0.3-4.3 mg/kg, intravenously) inhibited electrically induced contractions of the vas deferens of pithed rats. In the presence of the selective alpha 2-adrenoceptor antagonist idazoxan (1 mg/kg, intravenously) desipramine potentiated nerve stimulation. Although idazoxan (10-1440 micrograms/kg, intravenously) itself potentiated electrically induced contractions of the vas deferens the potentiation observed was markedly less than that obtained in rats pretreated acutely with desipramine (0.3 mg/kg, intravenously). Acute simultaneous blockade of both prejunctional alpha 2-adrenoceptors and uptake into nerve terminals can produce maximal potentiation of the contraction of the vas deferens to sympathetic nerve stimulation. Results are discussed in relation to the hypothesis that the combination of an uptake inhibitor and a prejunctional alpha 2-adrenoceptor antagonist, by enhancing noradrenergic transmission, may provide an antidepressant therapy with rapid onset of action.
Doxey
J C
JC
Roach
A G
AG
Samuel
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D003891:Desipramine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D019329:Idazoxan; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D003891:Desipramine; D019329:Idazoxan