m-trifluoromethylphenylpiperazine and m-chlorophenylpiperazine-induced hypothermia in mice is reversed by tricyclic antidepressants and other drugs.
Many antidepressants reverse arylpiperazine-induced hypothermia after acute treatment by a mechanism that does not seem to implicate monoamine uptake inhibition. Activity is found in reversing 1-(m-trifluoromethylphenyl)piperazine (TFMPP)-induced hypothermia by desipiramine 5 and 10 mg/kg and not by maprotiline 10 and 20 mg/kg. Clomipramine and fluoxetine with comparable serotonin uptake blocking potential do not have comparable TFMPP-reversing effects. A dibenzothiadiazepine compound (IM/P/3/4), hypothesized to have antidepressant activity though devoid of uptake blocking properties, was active at 10 and 20 mg/kg. Other classes of tricyclics such as neuroleptics (clozapine 5 and 10 mg/kg) and chlorpromazine (2 and 10 mg/kg) and the H1 antihistamines, promethazine (20 mg/kg) and cyproheptadine (10 mg/kg) are active, as well as the calcium antagonists nifedipine (10 mg/kg) and verapamil (10 mg/kg). We hypothesize that properties other than monoamine-uptake block which these compounds share (such as calcium-uptake inhibition) could be involved. Activity was also seen with the 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, at 0.05 and 0.25 mg/kg), and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT at 3 mg/kg) as well as with the muscarinic agonist oxotremorine (0.1 mg/kg).
A. Menarini Farmaceutici s.r.1., Pharmacological Research Division, Florence, Italy.
G
G
Volterra
C
C
Cutrufo
A
A
Lecci
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D010879:Piperazines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C018406:1-(3-trifluoromethylphenyl)piperazine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid