Oxaprotiline enantiomers stimulate ACTH and corticosterone secretion in the rat

Abstract

The effect of oxaprotiline (OXA) enantiomers--of which (+)-OXA inhibits noradrenaline (NA) uptake, whereas (-)-OXA does not--on the secretion of adrenocorticotropin hormone (ACTH) and corticosterone was studied in rats. Both enantiomers dose-dependently and with a similar potency increased the plasma level of ACTH and corticosterone, the effect of (-)-OXA on corticosterone being of a longer duration. The stimulation of ACTH secretion and the inability of (+)- and (-)-OXA to increase the plasma corticosterone concentration in animals pretreated with dexamethasone indicate that secretion of the latter hormone results from the action of the enantiomers at a level superior to the adrenal cortex, i.e. the hypothalamus/pituitary. The corticosterone response to (+)- or (-)-OXA was not modified in rats with a selective lesion of NA nerve endings induced by the neurotoxin DSP-4, nor was it affected by the selective alpha 1-antagonist prazosin, the selective alpha 2-antagonist yohimbine, the mixed alpha 1/alpha 2-antagonist phentolamine, the selective dopamine (D2) receptor antagonist sulpiride and the non-selective 5-hydroxytryptamine (5-HT) receptor antagonist metergoline. These results indicate that neither the NA system nor D2 and 5-HT receptors are involved in the hormonal response to the OXA enantiomers. Although the (+)- and (-)-OXA-induced stimulation of corticosterone secretion was not antagonized by diazepam, ipsapirone, naloxone, or propranolol, it cannot be excluded that both these enantiomers act as non-specific stressors.