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The use of the plasma concentration-effect relationship as a tool for the study of the mechanism of action of naloxone effects on mood and endocrine function

Departamento de Psico-Neuroendocrinologia, Instituto Mexicano de Psiquiatría, Calz. Mexico-Xochimilco 101, Tlalpan, 14370 México, D.F.

Vinicio Granados-Soto

Sección de Terapéutica Experimental, Departamento de Farmacologia y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F.

Patricia Aguirre-Bañuelos

Sección de Terapéutica Experimental, Departamento de Farmacologia y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F.

Mario Cárdenas

Departamento de Biologia de la Reproducción, Instituto Nacional de la Nutrición 'Salvador Zubirán', Mexico, D.F.

Gilberto Castañeda-Hernández

Sección de Terapéutica Experimental, Departamento de Farmacologia y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F.

The relationship between naloxone-plasma concentrations and their effects on mood and endocrine function was studied. Ten healthy volunteers received 1.0 mg/kg i.v. naloxone or placebo following a randomized double- blind design. Effects on mood, determined by a visual analogue scale and luteinizing hormone (LH) and naloxone-plasma concentrations were measured at selected times. Naloxone induced significant effects on confusion, bewilderment and indifference, and an increment in LH levels. The timecourse of the responses on confusion and bewilderment was similar to that of naloxone-plasma concentration, suggesting that these effects are directly related to the action of naloxone on its receptors. Responses for indifference and LH, however, exhibited a delayed onset. This delay could be due to an indirect action, i.e. to the participation of additional physiological mechanisms in a cascade-like manner. The results show that analysis of the concentration-effect relationship can be a useful tool for understanding naloxone effects on mood and endocrine function.

Key Words: concentration-effect relationship • endocrine function • endogenous opioid system • mood • naloxone

Journal of Psychopharmacology, Vol. 11, No. 4, 361-365 (1997)
DOI: 10.1177/026988119701100413


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