O-19-3 - Refractory depression a biochemical hypothesis

Abstract

Ex vivo investigations were carried out to study the potentiating actions of the MAOIs moclobemide and tranylcypromine on peripheral a- and β-adrenergic effects of dopamine. Isolated rat vas deferens and atria were used. Preliminary experiments showed that both moclobemide and tranylcypromine did not affect the response to noradrenaline, while they enhanced the response to tyramine. By comparison of the responses to dopamine in control and reserpinized rats, it was shown that dopamine acts in a direct and indirect manner on both the tissues tested.Two concentrations (20, 40 mg/kg, i.p.) of moclobemide were tested and administered at different time periods (2, 5 or 24 h) before the animals were sacrificed. Two concentrations (2, 20 mg/kg, i.p.) of tranylcypromine were tested at different intervals of time (2, 24 h). The results obtained pointed out that: (1) Moclobemide 20 mg/kg potentiated the α-adrenergic response to dopamine only 2 h after administration while 40 mg/kg-exerted a potentiation which was evident not only 2 but also 5 h after administration. Both doses were ineffective 24 h after administration.(2) Moclobemide 20 and 40 mg/kg potentiated the β-adrenergic response to dopamine. The effect was present 2 and 5 h after administration but it was absent 24 h after.(3) Tranylcypromine20 mg/kg potentiated the α-adrenergic response to dopamine: this effect was present after 2 h from pretreatment and was still evident after 24 h. The lower concentration of tranylcypromine (2 mg/kg) enhanced the response to dopamine only after 24 h from pretreatment.(4) Tranylcypromine 20 mg/kg enhanced the β-adrenergic response to dopamine: this effect was present 2 h after pretreatment and lasted 24 h after pretreatment. The same results were obtained with tranylcypromine 2 mg/kg.Therefore there is strong evidence of differences between moclobemide and tranylcypromine in the time course of their enhancing effects of α- and β-adrenergic responses to dopamine.