Interaction of antidepressants with 4-aminopyridine.

Systemic administration of 4-Aminopyridine at a dose of 4 mg/kg (4-AP) induces hypothermia in mice. Scopolamine (ED50 = 0.26 mg/kg) and two tricyclic antidepressants, desipramine (ED50 = 1.

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.

Potential antidepressant activity and enhancement of serotonin uptake of a new dibenzothiadiazepine derivative.

A molecule, 6-methyl-6,11-dihydro-11-[(N,N-dimethylamino) acetyl]dibenzo[c,fl-[1,2,5]thiadiazepine 5,5-dioxide, (IM/P/3/4, CAS 128377-70-8), was identified in a screening program, which had the scope of finding compounds with antidepressive potential without the common sideeffects of existing antidepressive medication. IM/P/3/4 was found active a) in antagonizing apomorphine (16 mg/kg) and reserpine-induced hypothermia in mice; b) in potentiating yohimbine-induced lethality in mice; c) in reducing immobility of rats forced to swim and of mice suspended by the tail. IM/P/3/4 does not affect a) apomorphine-induced stereotypy; b) amphetamine-induced hypermotility; c) haloperidol-induced catalepsy and water-induced grooming and d) does not induce stereotypy or alter motor activity.

New dibenzothiadiazepine derivatives with antidepressant activities.

A new series of 11-[(aminoalkyl)carbonyl] derivatives of 6,11-dihydrodibenzo[c,f][1,2,5]thiadiazepine 5,5-dioxide (10-39) were synthesized and evaluated for potential antidepressant activity in the apomorphine-induced hypothermia (Apo 16) test. Effects on reserpine-induced hypothermia and toxicity for the most potent antagonists of Apo 16 hypothermia were also studied. Structure-activity relationships are reported.

Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia.

Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip).