effect of sympathetic antagonists on the antidepressant action of Alprazolam

Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam-induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone [atenolol, a beta1-selective adrenoceptor antagonist; propranolol, a non selective [beta-adrenoceptor antagonist; and prazocin, an al-adrenoceptor antagonist]. Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments.In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates beta2 receptors to produce an antidepressant action. Imipramine may act by activating beta2 receptors by blocking or down-regulating beta1 receptors

Effects of calcium channel blockers on antidepressant action of alprazolam and imipramine

Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups [n = 7 per group]. One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone [alprazolam or imipramine]; two groups each received a single dose of the calcium channel blocker [nifedipine or verapamil]; four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant [with same doses used for either in the previous four groups]. Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect [delay the onset of immobility] when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine [additive antidepressant effect]. This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms