Potential antidepressant activity and enhancement of serotonin uptake of a new dibenzothiadiazepine derivative
Borsini, F.; Volterra, G.; Lecci, A.; Evangelista, S.; Mancinelli, A.; Cutrufo, C.; Parlani, M.; Mennini, T.; Barone, D.; Meli, A.
Arzneimittel-Forschung 41(6): 573-580
1991
ISSN/ISBN: 0004-4172 PMID: 1718290 Document Number: 382060
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 side-effects 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 stereotype or alter motor activity. The compound also a) reduced the beating of rat right heart atria only at a concentration of 3 .times. 10-4 mol/l; b) had weak anticholinergic activity; c) antagonized electroshock-induced convulsions and d) prevented indometacin-induced duodenal ulcers. IM/P3/4 does not have good affinity for noradrenergic, serotonergic, dopaminergic, histoaminergic or muscarinic receptors and does not displace imipramine, desipramine and mianserine from their binding sites. IM/P/3/4 increases 5-hydroxyindolacetic acid content and 3H-serotonin uptake in the hypothalamus. The present results suggest that IM/P3/4 is a potential antidepressant with reduced side effects and with a mechanism of action which is different from that of other antidepressants.