NEW N-(BENZHYDRYLOXYALKYL)-4-(CARBOXY CARBAMOYLMETHYL) PIPERIDINE-DERIVATIVES WITH ANTIDEPRESSANT ACTIVITY/

Several benzhydryloxylalkylpiperidine derivatives were prepared with t he aim of obtaining new antidepressant compounds. The influence of the length of the aliphatic chain and of aromatic and piperidine ring sub stitutions was studied. The pharmacological activity of compounds was investigated in vivo by means of a screening comprising four pharmacol ogical tests: antagonism of reserpine and apomorphine hypothermia; inc rease of yohimbine induced mortality; and antagonism of immobility in tail suspension test. An in-depth pharmacological study was performed with the more active compounds and a binding study to serotonin (5-HT) , norepinephrine (NE) and dopamine (DA) reuptake sites was performed f or the preferred compounds. The most active compounds [+], [-]-cis-31, 32 and 46 exhibited an interesting psychopharmacological profile afte r intraperitoneal administration. This profile was confirmed by the or al route for 31 and 46. In vitro, these compounds showed a non-selecti ve inhibition of DA, NE and 5-HT uptake.