5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: a novel 5-HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral activity.

The preparation of a series of conformationally restricted analogues of indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines, is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5-HT2C receptors were determined. Of these compounds, the 1,2,3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high affinity for the 5-HT2C (pKI 8.0) and 5-HT2B receptors (pA2 8.5), with excellent selectivity over the 5-HT2A and various other receptors (pKI < 6). 11 is also considerably more active than 1 in both an in vitro functional model, 5-HT-stimulated phosphoinositol hydrolysis (pKB 8.8), and an in vivo functional model, mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5-HT2C receptors.

The effect of oral oxidised copper wire on liver copper in farmed red deer.

Twenty-two weaner red deer stags grazed on a marginally copper-deficient property were used to evaluate the effect on liver copper levels of log oxidised copper wire particles given orally. The deer were assigned to two groups on the basis of pre-trial liver copper levels, and grazed together for the duration of the trial from March to October. Liver biopsies were collected from treated and control deer on six occasions at monthly intervals and were analyzed for copper content. Mean liver copper in the treated group rose from pre-treatment levels of 101.8 micromol/kg to a peak of 849.6 micromol/kg two months after copper administration. Thereafter, levels fell steadily until six months after administration when they averaged 84.8 micromol/kg. The mean liver copper content of untreated deer rose from 102.7 micromol/kg at the commencement of the trial, peaked at 255.3 micromol/kg after two months, fell to 103 micromol/kg one month later and remained low thereafter. The liver copper content in treated deer was significantly higher than for control deer for the duration of the study (p<0.01 for months 14 and 6, p <0.05 for month 5). It is concluded that log oxidised copper wire particles acted to provide adequate liver copper stores for up to five months in deer grazed on a marginally copper-deficient property.

Congenital absence of the breast.

A case of unilateral absence of the breast and nipple in a male, accompanied by partial absence of the pectoralis major muscle, is discussed.