Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--III. Hypothalamo-pituitary-adrenocortical axis.
In this report the effects of various receptor blockers on the desimipramine (DMI)-induced cortisol (ACTH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker, i.e. methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). In addition, the effect of prazosin on DMI-induced ACTH stimulation was examined. DMI-induced cortisol stimulation was not significantly different after DMI alone (n = 12) from that after three days pretreatment with methysergide (12 mg p.o.) in another group of subjects (n = 12). Neither the combination of DMI plus propranolol (15 mg i.v. n = 18, incomplete block design) nor that of DMI plus phentolamine (60 mg i.v. n = 12) had a significant influence on DMI-induced cortisol secretion. Following combined administration with yohimbine (10 mg i.v.), cortisol secretion was higher compared to that after DMI alone in the same group (n = 6). DMI-induced cortisol secretion was significantly lower (p less than 0.01) following combined administration with prazosin (1 mg p.o. n = 12), as was DMI-induced ACTH secretion (p less than 0.05) in these subjects. The findings of these trials, especially those of the prazosin trial, indicate that DMI-induced stimulation of cortisol and ACTH secretion is attributable to the noradrenaline (NA) reuptake inhibiting effect of DMI, and that the stimulus is transmitted with the aid of noradrenergic alpha-1 receptors. Alpha-2 receptors possibly exert a negative influence on this effect.
D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002352:Carrier Proteins; D003891:Desipramine / Q000494:pharmacology*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010907:Pituitary Hormones / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D001786:Blood Glucose; D002352:Carrier Proteins; D010907:Pituitary Hormones; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; C036079:desipramine receptor; D015016:Yohimbine; D011433:Propranolol; D003891:Desipramine; D011224:Prazosin; D008784:Methysergide; D010646:Phentolamine