Resolved 3-(3-Hydroxyphenyl)-N-n-propylpiperidine and its analogs: central dopamine receptor activity
| Autor: | Seth-Olov Thorberg, U. Hacksell, J. L. G. Nilsson, Domingo Sanchez, Per Olov Lindberg, L.-E. Arvidsson, Johansson Am, Håkan Wikström, Stephan Hjorth, Kjell A. Svensson |
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| Rok vydání: | 1984 |
| Předmět: |
Male
Serotonin Reserpine Tertiary amine Intrinsic activity Stereochemistry Motor Activity Receptors Dopamine Norepinephrine Piperidines X-Ray Diffraction Postsynaptic potential Dopamine Drug Discovery medicine Animals Receptor Chromatography High Pressure Liquid Chemistry Rats Inbred Strains Biological activity Receptors Adrenergic alpha Dihydroxyphenylalanine Rats Dopamine receptor Autoreceptor Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 27:1030-1036 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Seven enantiomeric pairs of N-alkyl analogues of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP, 12) have been synthesized and evaluated pharmacologically (biochemistry and behavior) in order to examine their ability to interact with central dopamine (DA) receptors, particularly DA autoreceptors. In the R series it seems as if all compounds behave as classical DA receptor agonists with affinity and intrinsic activity for both pre- and postsynaptic receptors. The same bifunctional profile seems to be valid for the S enantiomers with N-substituents larger or bulkier than n-propyl. Likewise, the S enantiomers with ethyl or n-propyl N-substituents seem to have affinity for both pre- and postsynaptic receptors. In the total series, (S)-(-)-3-PPP [(S)-12] seems to be the most interesting compound both from the theoretical and the therapeutical point of view, possibly attenuating DA function in two different ways by stimulating the presynaptic receptors and blocking the postsynaptic receptors. This compound has been selected for extended pharmacological studies as a potential antipsychotic drug. |
| Databáze: | OpenAIRE |
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