Nontricyclic antidepressant agents derived from cis- and trans-1-amino-4-aryltetralins
| Autor: | Willard M. Welch, R. Sarges, A. R. Kraska, B. K. Koe |
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| Rok vydání: | 1984 |
| Předmět: |
Male
Serotonin Serotonin uptake Tetrahydronaphthalenes Dopamine Naphthalenes Pharmacology Norepinephrine Isomerism X-Ray Diffraction Drug Discovery medicine Animals chemistry.chemical_classification Rats Inbred Strains Stereoisomerism Biological activity Antidepressive Agents In vitro Rats Biochemistry chemistry Molecular Medicine Antidepressant Cis–trans isomerism Synaptosomes medicine.drug Tricyclic |
| Zdroj: | Journal of Medicinal Chemistry. 27:1508-1515 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00377a021 |
| Popis: | The need for drugs that lack the obtrusive and limiting side effects of the tricyclic antidepressants has prompted the search for agents with greatly enhanced selectivity for specific mechanisms believed to be essential for antidepressant efficacy. The potential role of derangements of 5-HT pathways in the etiology of depression has long been suspected and has given impetus to the development of newer compounds that accentuate inhibition of serotonin reuptake. This paper presents structure-activity relationships for a series of cis-1-amino-4-(substituted-aryl)tetralins, which are surprisingly potent and selective inhibitors of serotonin uptake in in vitro models. These compounds are pharmacologically distinct from corresponding members of the trans series, which also potently block uptake of dopamine and norepinephrine. The activity in both cis and trans series is stereospecific, being restricted to the cis-(1S,4S) and the trans-(1R,4S) enantiomers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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