Effect of p‐Chlorophenylalanine and α‐Methyltyrosine on the Antinociceptive Effect of Antidepressant Drugs

Abstract: The role of para‐chlorophenylalanine and α‐methyl‐DL‐p‐tyrosine in the antinociceptive effects of the intracerebroventricular administration of the antidepressant drugs clomipramine, zimelidine, imipramine and maprotiline was studied using the acetic acid writhing test in mice. The results demonstrated an antinociceptive effect for all these antidepressants. Pretreatment with para‐chlorophenylalanine significantly reduced the antinociception induced by the ED₅₀'s of imipramine and maprotiline, and did not modify the effects of zimelidine and clomipramine, pretreatment with α‐methyltyrosine did not modify the antinociception induced by these drugs except maprotiline. Pretreatment with para‐chlorophenylanine plus α‐methyltyrosine significantly reduced the antinociceptive effect of all the antidepressants tested. The main finding of the present study is that the association of para‐chlorophenylanine plus α‐methyltyrosine reduced the antinociceptive action of all the antidepressants. This means that critical levels of both 5‐HT and NA are responsible for mediating the antinociceptive effects of antidepressants on the writhing test in mice. 1995 Nordic Pharmacological Society