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A new nontricyclic antidepressant agent. Synthesis and activity of N-[trans-2-(dimethylamino)cyclopentyl]-N-(3,4-dichlorophenyl)propanamide and related compounds.

A series of new nontricyclic antidepressant compounds was synthesized. A representative of this class is compound 6. Five structural parameters were investigated: ring size, cis/trans stereochemistry, amide substitution, aromatic substitution, and amine substitution. The pharmacological tests employed, indicative of antidepressant activity, were yohimbine potentiation test, oxotremorine antagonism test, and apomorphine potentiation test. Structure--activity relationship is discussed.

Animals↗

2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents.

A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones was prepared and evaluated for potential antidepressant activity. Members of this series were generally prepared by the alkaline ring closures of the corresponding 1-aroylthiosemicarbazides. Several members of this series were potent antagonists of both RO 4-1284-induced hypothermia and reserpine-induced ptosis in mice. In general the more active members of this series were substituted by haloaryl groups at the 5-position of the triazole nucleus and by methyl groups at the 2- and 4-positions. Exchange of the thiocarbonyl group at the 3-position for a carbonyl group resulted in the complete loss of activity. Biochemical evaluation of the more active members of this series indicated that the aforementioned activities were not a consequence of either norepinephrine (NE) uptake or monoamine oxidase inhibition. In an attempt to determine a mechanism of action, one member of this series, compound 22, was selected for further evaluation in an electrophysiological model where it was found to reduce norepinephrine function in the cerebellum as measured by the NE augmentation of GABA inhibition of Purkinje neurons.

Animals↗

Economic evaluation of antidepressive agents: a systematic critique of experimental and observational studies.

The purpose of this study was to examine whether experimental and observational pharmacoeconomic analyses of antidepressant drugs support the choice of one of the selective serotonin reuptake inhibitors or newer antidepressants as first-line treatment for patients with major depression. We systematically reviewed economic evaluations of two or more antidepressants completed in clinical practice. A systematic electronic search yielded 38 studies meeting the inclusion criteria, of which 23 were administrative database analyses, 12 were observational studies, and 3 were randomized clinical trials. Experimental data indicated that tricyclic antidepressants are equivalent to selective serotonin reuptake inhibitors in terms of total expenditure. While the database analyses are susceptible to bias and confounding variables, they provided an added dimension based on observations from everyday clinical practice. The majority of these studies failed to show any significant difference. Taken together, available pharmacoeconomic studies indicate that tricyclic drugs and selective serotonin reuptake inhibitors have similar cost effectiveness in the health care systems where these comparisons have been made.

Antidepressive Agents↗

[Therapy with neuroleptics and antidepressive agents: a fundamental and critical discussion from a biological viewpoint].

This paper presents a critical discussion on fundamental questions of treatment with neuroleptic and antidepressant drugs on the basis of current knowledge in the biological psychiatry and clinical psychopharmacology. The issues raised are some problems in the definition of the terms "neuroleptic" and "antidepressant" drugs, the indications for treatment with neuroleptic and antidepressant drugs and a definition of the term "therapeutic efficacy" of neuroleptic and antidepressant drugs.

Antidepressive Agents↗