Pharmacodynamic profile of CQP 201-403, a novel 8 alpha-amino-ergoline.

The profile of action in animals of CQP 201-403, a novel 8 alpha-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and be more potent than bromocriptine (Parlodel).

In vivo labeling of brain dopamine D2 receptors using the high-affinity specific D2 agonist [3H]CV 205-502.

The high-affinity selective dopamine D2 agonist [3H]CV 205-502 was utilized to in vivo label brain dopamine D2 receptors in the rat. Intravenous administration of [3H]CV 205-502 resulted in a selective accumulation of radioactivity in the striatum and in the pituitary. Smaller amounts of binding were found in the hypothalamus and cortex and non-significant binding was seen in the cerebellum.

Binding studies with [3H]cis-methyldioxolane in different tissues. Under certain conditions [3H]cis-methyldioxolane labels preferentially but not exclusively agonist high affinity states of muscarinic M2 receptors.

Special conditions--tricine buffer containing Ca2+ and Mg2+, 22 degrees C (TCM)--allow to label a much higher proportion of muscarinic receptors by [3H]cis-methyldioxolane (CD) than hitherto described (Vickroy et al. 1984a). Taking the maximum number of binding sites, Bmax, of [3H]QNB as 100%, Bmax of [3H]CD amounts to 83% in the rat heart instead of the reported 17%, 33% in the cerebral cortex instead of 6%, 20% in hippocampus and 55% in pons/medulla.

[3H]ketanserin labels 5-HT2 receptors and alpha 1-adrenoceptors in human and pig brain membranes.

The binding characteristics of [3H]ketanserin (a reported selective radioligand for serotonin 5-HT2 receptors) and [125I]BE 2254 (which labels selectively alpha 1-adrenoceptors) were characterized in brain frontal cortex membranes of pig and man. Saturation experiments indicated that both radioligands label apparently a homogeneous class of binding sites in human and pig fontal cortex membranes. Competition experiments with [125I]BE 2254 using 17 agonists and antagonists showed monophasic and steep curves in human and pig frontal cortex membranes.