The effect of amitriptyline on presynaptic mechanisms in noradrenergic nerves

Electrically evoked and resting overflow of tritium was measured from mouse vas deferens previously incubated with [3H]-(-)-noradrenaline. At low concentrations (1.6 x 10-7 to 4 x 10-6M) amitriptyline increased only the evoked tritium overflow while higher concentrations increased both evoked and resting overflow. In the presence of atropine (1 x 10-6M) amitriptyline still produced an increase in evoked tritium overflow. In the presence of a concentration of cocaine (1.1 x 10-5M) which produced a maximal blockade of the uptake of exogenous noradrenaline the application of amitriptyline still produced an increase in evoked tritium overflow. In the presence of a concentration of phentolamine (1 x 10-5M) that produced complete blockade of the presynaptic α-adrenoceptors, amitriptyline still produced an increase in evoked tritium overflow. In the presence of cocaine and phentolamine together the effect of amitriptyline on evoked overflow was abolished. It is concluded that amitriptyline may raise synaptic levels of noradrenaline by blocking presynaptic α-adrenoceptors controlling noradrenaline release and by blocking its uptake into sympathetic neurones. (author)