Mesaton (phenylephrine) Potentiates the Antidepressant and Eliminates the Sedative Action of Amitriptyline in Rats

Abstract

Single i.m. doses of amitriptyline (10–30 mg/kg) induced a mild antidepressant effect in rats, decreasing immobility in the Porsolt test by factors of no more than 1.3–1.7. These doses of amitriptyline had significant sedative effects, as they decreased horizontal activity in the open field by factors of 3–6 and reduced vertical activity by factors of 2–2.5. Combined single i.m. administration of a low dose of amitriptyline (3 mg/kg) or a high dose of amitriptyline (30 mg/kg) combined with Mesaton (phenylephrine) at a threshold dose of 0.02 mg/kg (ineffective when given alone), induced a maximum antidepressant effect, decreasing immobility in the Porsolt test by factors of 3 and 4.6 respectively, but had no sedative side effect in the open field. The mechanism of potentiation of the antidepressant effect and elimination of the sedative effect of amitriptyline appears to be based on stimulation of gastric mucosal afferents by Mesaton.