Selective blockade of the serotonin 5-HT(2A) receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT(2A) receptor using AutoDock. Selected compounds with high in silico binding affinities were screened in vitro using radioligand-binding assays against rat serotonin (5-HT(1A) and 5-HT(2A)) and dopamine (D1 and D2) receptors. (R)-Roemerine and (±)-nuciferine were found to have high affinity for the 5-HT(2A) receptor (K(i) = 62 and 139 nM, respectively), with (R)-roemerine showing 20- to 400-fold selectivity for the 5-HT(2A) receptor over the 5-HT(1A), D1 and D2 receptors. Investigation into the ligand-receptor interactions suggested that the selectivity of (R)-roemerine is due to it having stronger H-bonding and dipole-dipole interactions with several of the key residues in the 5-HT(2A) receptor-binding site.
β-Hydroxylase deficiency accounts for 7% of all cases of congenital adrenal hyperplasia (CAH), with an incidence of 1 in 100,000 live births [1]. It occurs due to mutation in the 11-β-hydroxylase (CYP11B1) gene that results in loss of enzyme activity and a block in the conversion of 11-deoxycortisol to cortisol, leading to cortisol deficiency. The loss of negative feedback on adrenocorticotrophic hormone (ACTH) secretion leads to enhanced ACTH mediated adrenal androgen synthesis. Clinical features in a female baby, therefore, consist of virilization of the external genitalia and genital ambiguity. Milder cases can manifest later in childhood or in young adults. The principal differentiating feature from 21-hydroxylase deficiency is hypertension, which is thought to be secondary to the mineralocorticoid effect of excess deoxycorticosterone (DOC). CASE REPORTWe report a 7-year-old girl, who was brought by her mother, with the chief complaint of change in the girl's voice to adult male voice. The child was a product of a non-consanguineous marriage and the only child to her parents and there was no history of miscarriages or intrauterine deaths. She was born of normal vaginal delivery at term gestation. There was no history of neonatal seizures, hypoglycemia, sepsis, or salt wasting crisis.Developmental history was normal. Her mother noticed change in her voice that progressed to a male voice, over a period of 2 months. On probing, mother revealed the presence of phallus like structure noticed in infancy, which progressively increased in its size. There was history of increased skin pigmentation from infancy. The girl developed axillary and pubic hair at an age of 4 years. There was no history of weight loss, loss of appetite, pain abdomen, or vomiting.The general physical examination revealed hyperpigmentation over face, palmar creases, knuckles, and gums. Her skin was greasy with acne (Fig. 1). The girl had a low-pitched voice similar to that of a pubertal boy. Her pulse rate was 93/min, blood pressure (BP) was 130/80 mm Hg. Hypertension was confirmed after checking blood pressure three times on different days. Her height was 127 cm (75 th -90 th centile), weight was 23 kg (50 th centile), and sexual maturity rating was B1 A2 P3. External genital examination revealed clitoromegaly (2.6 cm in length), single urogenital orifice and partially fused labioscrotal swellings (Prader's stage-3). Other systems were found normal on examination.The base line investigations such as complete blood count, serum creatinine, electrolytes, and blood glucose were normal. Bone age was advanced (11 years). Ultrasound abdomen revealed bilateral prominent suprarenal glands measuring 10 mm × 7.9 mm on the right side and 10 mm × 9 mm on the left side. Karyotype was 46 XX. Basal 17-α-hydroxyprogesterone level was 14.6 ng/ml and post Synacthen stimulation, the
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