Oxaprotiline enantiomers stimulate ACTH and corticosterone secretion in the rat.
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.
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
E
E
Przegaliński
B
B
Budziszewska
A
A
Grochmal
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood*; D003907:Dexamethasone / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives* / Q000494:pharmacology; D008711:Metergoline / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology; D013237:Stereoisomerism; D013469:Sulpiride / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D001596:Benzylamines; D010880:Piperidines; D011743:Pyrimidines; D012702:Serotonin Antagonists; D013566:Sympathomimetics; D008711:Metergoline; D008376:Maprotiline; D009270:Naloxone; C027299:hydroxymaprotilin; C015613:4-(5,6-dimethyl-2-benzofuranyl)piperidine; C043077:ipsapirone; D013469:Sulpiride; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; C012102:DSP 4; D003975:Diazepam; D003345:Corticosterone