Abstract
1 The effect of various antidepressants (5 × 10-8 to 2 × 10-5 M) on the resting overflow of tritium, on the evoked overflow and the contractile response to electrical stimulation (2.5 Hz, 2.0 ms) has been determined in mouse vas deferens previously incubated with [3H]-(—)-noradrenaline.
2 Mianserin and ORG GC 94 produced a concentration-dependent increase of more than two fold in the electrically evoked overflow and the contractile response and, at the highest concentration, slightly increased resting release. These effects were largely unchanged in the presence of a concentration of cocaine effective in blocking noradrenaline uptake (1.1 × 10-5 M).
3 The ability of phentolamine (1 × 10-5 M) to increase both the evoked overflow of tritium and the contractile response was greatly reduced when these parameters were already elevated by the presence of mianserin or ORG GC 94.
4 The inhibitory effect of exogenous (—)-noradrenaline on evoked overflow was greatly reduced in the presence of mianserin or ORG GC 94 (4 × 10-6 M).
5 The inhibitory effect of clonidine on the twitch response of the mouse vas deferens was antagonized by mianserin and ORG GC 94 in a competitive manner (pA2 values 7.3 and 7.1 respectively).
6 Maprotiline, desipramine and nortriptyline (> 3 × 10-6 M) produced a parallel fall in both evoked tritium overflow and in the contractile response and increased the resting overflow at higher concentrations. These effects were largely unchanged in the presence of cocaine (1.1 × 10-5 M).
7 Doxepin, imipramine and iprindole all increased resting overflow at high concentrations (2 × 10-5 M) but produced only small changes in evoked overflow and in the contractile response at lower concentrations.
8 It is concluded that mianserin and ORG GC 94 produce a blockade of presynaptic α-adrenoceptors which could contribute to an antidepressant effect but that this type of action is not common to all antidepressants.
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