Stimulation of Vagus By Phenylephrine Increases the Efficiency and Safety of Antidepressants and Anti-Epileptics

Background: Earlier, we discovered the possibility of potentiation of the therapeutic effects of small (threshold) doses of CNS agents by phenylephrine and adrenaline, while eliminating their side effects. However, the question of the possibility of potentiation by phenylephrine and other CNS potentiators of high therapeutic doses of CNS agents remained unstudied. This study is devoted to the research of this problem. Objective: The aim of the study was to investigate the effect of the threshold dose of phenylephrine on the antidepressant effect of amitriptyline and the anticonvulsant effect of diazepam, as well as their side sedation in high doses. Method: The experiments were carried out on the animated models of depression (Porsolt test) and epilepsy (clonic pentylenetetrazole (PTZ)-induced seizures), resistant to antidepressants and antiepileptics even at high therapeutic doses. Side sedative effect of substances was evaluated in the "open field" test. Results: We established that the stimulation of gastric vagal afferents with phenylephrine, when administered orally at threshold doses, potentiates the anticonvulsant effect of diazepam and the antidepressant effect of amitriptyline in high therapeutic doses to the maximum level that is impossible in their application by themselves, and at the same time eliminates their side sedation. Conclusion: A synergistic effect of phenylephrine and CNS drugs on the peripheral and central links of the vagal stress-protective reflex is discussed. It is assumed that the potentiation of therapeutic effect by phenylephrine and the elimination of side effects of the CNS agents occurs as a result of strengthening the vagal stress-protective reflex, eliminating the drug stress.