The effect of amitriptyline on presynaptic mechanisms in noradrenergic nerves.
1 Electrically evoked and resting overflow of tritium was measured from mouse vas deferens previously incubated with [3H]-(--)-noradrenaline. 2 At low concentrations (1.6 X 10(-7) to 4 X 10(-6)M) amitriptyline increased only the evoked tritium overfow while higher concentrations increased both evoked and resting overflow. 3 In the presence of atropine (1 X 10(-6 M) amitriptyline still produced an increase in evoked tritium overflow. 4 In the presence of a concentration of cocaine (1.1 X 10(-5) M) which produced a maximal blockade of the uptake of exogenous noradrenaline the application of amitriptyline still produced an increase in evoked tritium overflow. 5 In the presence of a concentration of phentolamine (1 X 10(-5) M) that produced complete blockade of the presynaptic alpha-adrenoceptors, amitriptyline still produced an increase in evoked tritium overflow. 6 In the presence of cocaine and phentolamine together the effect of amitriptyline on evoked overflow was abolished. 7 It is concluded that amitriptyline may raise synaptic levels of noradrenaline by blocking presynaptic alpha-adrenoceptors controlling noradrenaline release and by blocking its uptake into sympathetic neurones.
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009420:Nervous System / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D014649:Vas Deferens / Q000294:innervation
D000639:Amitriptyline; D001285:Atropine; D003042:Cocaine; D009638:Norepinephrine; D010646:Phentolamine