DIFFERENTIAL STEREOSELECTIVITY OF METHOTRIMEPRAZINE ENANTIOMERS FOR SELECTED CENTRAL NERVOUS-SYSTEM RECEPTOR TYPES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 21  (2) , 315-319
Abstract
Optical isomers of methotrimeprazine, an analgesic/neuroleptic, were investigated with respect to their ability to interact with 6 receptor types or subtypes. Bovine caudate nucleus tissue homogenates provided the dopamine, opiate and serotonin receptor populations studied. The radioligands used in saturation and binding competition experiments were 3H-dopamine, spiperone, dihydromorphine, 5-L-methionine enkephalin, naloxone and 5-hydroxytryptamine. Saturation experiments verified acceptable performance of these in vitro receptor assay systems and indicated that a 1-site binding model was adequate for each of these ligands. The competition experiments exhibited statistically significant (P < 0.05) differences in isomeric effects only for dopamine and 5-hydroxytryptamine receptors. The more active isomer, l-methotrimeprazine, was pharmacodynamically equivalent to chlorpromazine at these receptor types. When the magnitude of receptor stereoselectivity is plotted against an estimate of the more active isomer''s affinity for that particular receptor, an excellent correlation is observed. This suggests that a high degree of stereoselectivity characterizes a highly specific drug/receptor interaction. Evidently, methotrimeprazine does not produce analgesia via a direct action upon opiate receptors.

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