(+/-)[125Iodo] cyanopindolol (ICYP) is a radioligand which binds with an extraordinarily high affinity and specificity to beta-adrenoceptors. In contrast to (+/-) [125Ido]-hydroxybenzylpindolol (IHYP), the new ligand has neither affinity to alpha-nor to 5-HT-receptors. The dissociation constants of ICYP for beta- adrenoceptors in various tissues range from 27 to 40 pM, thereby exceeding the affinity of IHYP by a factor of approximately 3. ICYP does not discriminate between beta 1- and beta 2-adrenoceptors. Therefore, the densities of the two receptor subtypes can be determined from competition curves of ICYP by drugs previously found to show in vitro selectivity for beta 1-adrenoceptors. The guinea pig left ventricle contains only beta 1-adrenoceptors, whereas in a lung tissue, the ratio of beta 1-to beta 2-adrenoceptors is 1 to 4. The calculated affinities of five beta 1-selective antagonists for beta 1-adrenoceptors were nearly identical in the ventricle and the lung. Kinetic studies of ICYP binding to guinea pig lung membranes indicated that the dissociation reaction consists of two components, a fast process (t 1/2 = 9 min) and a slower process (t 1/2 = 8.8 h). A mathematical treatment revealed two possibilities of interpretation: 1. Two forms of the receptor exist which are interconvertible. 2. The (+)- and (-)- enantiomers of ICYP dissociate with different rate constants. The low dissociation constant of ICYP in combination with its high specific radioactivity (2175 Ci mmole -1) allows binding studies to be carried out with small protein and ligand concentrations, e.g. 3 microgram protein per assay in guinea pig lung membranes.

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The pharmacological properties of 6-cyclohexyl-2'-0-methyladenosine (SDZ WAG 994)-a potent, selective, and orally active adenosine A, receptor agonist-are described. SDZ W A G 994 is a potent (K, 23 +-2 nM, n = 5) and selective (1,090-fold vs. A2* receptors) displacer of binding to pig striatal A, receptors and behaves as a full agonist at the A , receptors coupled negatively to adenylate cyclase in rat adipocytes (pEC, , 6.4 * 0.2, n = 3), those which induce contraction of rat spleen (pEC, , 7.1 ? 0.1, n = 13) and those which suppress the response to autonomic nerve stimulation in guinea-pig ileum (PIC,, 6.6 * 0.1, n = 4) and rat kidney (PIC,, 6.0 ? 0.1, n = 6). The compound has negligible affinity (pEC,, < 4, n = 5) for the A, , receptor which mediates relaxation of guinea-pig aorta. In spontaneously hypertensive (SH) rats SDZ W A G 994, 0.05-0.5 mg/kg (0.141.4 pmolikg) PO, caused dose-related and sustained (> 5 h) falls in blood pressure (BPI and heart rate (HR) and suppressed plasma renin activity (PRA); the cardiovascular effects could be immediately and fully reversed by an intravenous injection of 8-(p-sulphophenyl)theophylline, 20 mg/kg (56.4 pmolikg). SDZ W A G 994 given via the food at 0.4 and 1.2 mg/kg/day (1.1 and 3.3 prnol/kg/day) for 7 or 14 days, respectively, induced dose-related hypotension and bradycardia which were well maintained throughout the treatment periods. In the conscious, normotensive dog, SDZ W A G 994, 1 and 3 rngikg (2.8 and 8.3 pmolikg) PO, induced substantial, sustained falls in BP which were accompanied by tachycardia. In salt depleted squirrel monkeys, SDZ W A G 994, 0.14.3 mg/kg (0.28-0.83 pmol/kg) iv or 0.24.6 mg/kg (0.56-1.7 pmol/kg) PO caused dose-related and sustained (> 5 h) bradycardia and suppression of PRA but no change in BP. In rhesus monkeys, SDZ W A G 994, 0.1-1.2 mg/kg (0.28-3.3 pmol/kg) PO induced sustained bradycardia and suppression of PRA and the plasma free fatty acid and triglyceride concentrations. The data establish SDZ WAG 994 as a potent, selective, and orally active adenosine A, receptor agonist with therapeutic potential in certain cardiovascular and/or metabolic disease states. o 1995 Wiley-Liss, Inc.

Brazilin and haematoxylin, plant pigments, were examined for their effects on the Bovine-Lens aldose reductase (LAR)-activity. About 50% inhibition was observed in a concentration of 10 (-4) M-brazilin and 10 (-4) M-haematoxylin, and above 95% inhibition was observed in a concentration of 10 (-3) M-brazilin and 10 (-3)M-haematoxylin. In order to determine the type of inhibition, kinetic studies were also conducted with brazilin and haematoxylin, in which both were found to be noncompetitive inhibitors.

Prolactin secretion inhibition and changes in striatal dopamine metabolism in rats were compared after the administration of 8 alpha-amino-ergoline CH 29-717 and 2 derivates. CQ 32-084 was similar to but less potent than CH 29-717, while 32-085, the l-methyl derivative, showed delayed dopaminomimetic effects.