The mechanism of the potentiating effect of antidepressant drugs on the protective influenc oe of diphenhydramine in experimental catatonia. The role of histamine.

The anticatatonic action of various antidepressants in moderate doses and their combination with sub-effective doses of diphenhydramine was correlated with brain histamine levels. The catatonia was induced by perphenazine with a concomitant and remarkable increase in the brain histamine level. Diphenhydramine partially protected the animals from the increase in brain histamine and mitigated the catatonia. The antidepressants, i.e. monoamine oxidase inhibitors and tricyclic antidepressants, partially protected animals both the increase in brain histamine and also the catatonia. The tricyclic antidepressants were, however, found to be more potent in both respects. The combination of sub-effective doses of monoamine oxidase inhibitors and diphenhydramine was effective in terminating experimental catatonia and the elevation of brain histamine while tricyclic antidepressants failed. A relationship between the duration of protection against catatonia and brain histamine level due to antidepressants alone and their combination with diphenhydramine was observed.