Effects of H1 antagonists on cholinomimetic-induced tremulous jaw movements: Studies of diphenhydramine, doxepin, and mepyramine

several previous studies, tremulous jaw movements in rats have been used to assess the effects of antiparkinsonian drugs and atypical antipsychotics. Because antihistamines such as diphenhydramine are used as antiparkinsonian agents, and atypical antipsychotic drugs such as clozapine and olanzapine have high affinity for histamine H1 receptors, the present study investigat ed the effects of H1 antagonists on cholinomimetic induced jaw movements. D iphenhydramine, doxepin, and mepyramine (all injected IP 2.5-20.0 mg/kg) we re assessed for their ability to block the jaw movements induced by 5.0 mg/ kg of the anticholinesterase tacrine. Within this dose range, only diphenhy dramine produced a robust and significant reduction in jaw movement activit y. Thus, diphenhydramine was subjected to further testing, which employed p rocedures previously used to assess the effects of other antitremorogenic d rugs, such as clozapine. Diphenhydramine did not induce jaw movement activi ty. In addition to suppressing jaw movement activity after acute injections , diphenhydramine also suppressed tacrine-induced jaw movements after repea led (14-day) administration. In summary, the present results show that diph enhydramine suppresses cholinomimetic-induced jaw movements, an effect that is similar to other antiparkinsonian or antitremorogenic drugs such as ant icholinergics, L-DOPA, DA antagonists, and clozapine. Nevertheless, doxepin produced only mild effects, and mepyramine, which has a higher affinity an d selectivity than diphenhydramine for H1 receptors, failed to suppress cho linomimetic-induced jaw movements. These results suggest that diphenhydrami ne suppresses tremulous movements through a mechanism that does not depend upon antagonism of histamine H1 receptors. (C) 2000 Elsevier Science Inc.