ABSTRACT
A series of new N-substituted derivatives of morphinan was synthesized and their binding affinity for the three opioid receptors (mu, delta, and kappa) was determined. A paradoxical effect of N-propargyl (MCL-117) and N-(3-iodoprop-(2E)-enyl) (MCL-118) substituents on the binding affinities for the mu and kappa opioid receptors was observed. All of these novel derivatives showed a preference for the mu and kappa versus delta binding.
Subject(s)
Morphinans/pharmacology , Receptors, Opioid, kappa/agonists , Receptors, Opioid, mu/agonists , Cocaine-Related Disorders/drug therapy , Drug Combinations , Humans , Morphinans/chemical synthesis , Morphinans/chemistry , Morphinans/therapeutic use , Narcotic Antagonists/pharmacology , Narcotic Antagonists/therapeutic use , Receptors, Opioid, mu/antagonists & inhibitorsABSTRACT
The aim of this study was to investigate hypothalamic-pituitary-adrenal (HPA) function in children with GH deficiency. Ninety-four patients were evaluated for GH deficiency and cortisol (F) deficiency using clinical criteria and L-dopa and insulin-induced hypoglycemia stimulation tests. They were assigned to three diagnostic groups: organic GH deficient (OGHD), idiopathic GH deficient (IGHD), and not GH-deficient (NGHD). Time series, cross-sectional, regression analysis revealed statistically significantly elevated F [>828 nmol/L (30 microg/dL)] in the OGHD group vs. the NGHD group. The value for F in the IGHD group was not different from the NGHD group. This finding suggests that dysregulation of the HPA axis is present in most children with OGH deficiency and significantly less often in children with IGH deficiency or without GH deficiency. Anatomical disruption of the control pathways for the HPA axis or stress may cause the dysregulation.
Subject(s)
Human Growth Hormone/deficiency , Hydrocortisone/blood , Blood Glucose/analysis , Child , Cross-Sectional Studies , Female , Humans , Hypoglycemia/blood , Hypoglycemia/chemically induced , Insulin , Levodopa , Male , Reference ValuesABSTRACT
The effects of L-dopamine (LD) administration and insulin-induced hypoglycemia in adrenocorticotropin (ACTH) and cortisol secretion were studied in 14 short boys. LD caused moderate changes in both hormones. The four boys with isolated, idiopathic growth hormone (GH) deficiency (IGD) demonstrated a greater cortisol increase in response to hypoglycemia than the 10 boys with normal GH secretion. In at least some short children with IGD, abnormal regulation of the hypothalamic-pituitary-adrenal axis may be present.
