Detail of "483-10-3"

Reference

Calcium influx-dependent and -independent a1-adrenoceptor-mediated processes of vasoconstriction in vivo do not operate via different a1-adrenoceptor subtypes

Calcium influx-dependent and -independent a1-adrenoceptor-mediated processes of vasoconstriction in vivo do not operate via different a1-adrenoceptor subtypes. Korstanje, Cornelis; Wilffert, Bob; De Jonge, Adriaan; Thoolen, Martin J. M. C.; Timmermans, Pieter B. M. W. M.; Van Zwieten, Pieter A. (Dep. Pharm., Univ. Amsterdam, Amsterdam 1018 TV, Neth.). J. Cardiovasc. Pharmacol., 6(6), 1102-8 (English) 1984. CODEN: JCPCDT. ISSN: 0160-2446. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 1 In pithed rats, the selective a1-adrenoceptor agonists St 587 [15327-38-5] and cirazoline [59939-16-1] show preponderant Ca influx-dependent and -independent vasoconstriction, resp. Using these agonists, selective (competitive) antagonists for either process of vasoconstriction were sought. For this purpose, antagonism was analyzed for 8 structurally different antagonists (prazosin [19216-56-9], BE 2254 [40077-13-2], AR-C239 [67339-62-2], R 28935 [55806-43-4], corynanthine [483-10-3], phentolamine [50-60-2], sulpiride [15676-16-1], and chlorpromazine [50-53-3]) opposing the pressor responses evoked by cirazoline and St 587. Where pA2 values (-log dose antagonist evoking a 2-fold shift for the agonist dose-response curve) could be calcd., no significantly different pA2 values against either agonist resulted. However, with respect to the slopes of the Schild plots, deviations from 1 were found for prazosin, R 28935, AR-C239, sulpiride, and chlorpromazine, but not uniformly against both agonists. Following treatment with phenoxybenzamine (PB) (30 mg/kg) and nifedipine (1 mg/kg), which produced Ca influx-sensitive and -insensitive vasoconstriction to cirazoline, resp., Schild plots were constructed for BE 2254, prazosin, and chlorpromazine. Using cirazoline as an agonist, unity slopes were now obtained for prazosin and chlorpromazine. The Schild plots of BE 2254 vs. cirazoline after PB or nifedipine administration, however, exhibited a slope deviating from 1. For prazosin and chlorpromazine, identical pA2 values still resulted against both processes of vasoconstriction to cirazoline. Evidently, a1-adrenoceptors mediating Ca influx-dependent and -independent vasoconstriction in vivo are not distinctly different entities, but are sep. recognition sites of the same receptor.

Structure affinity relationships for yohimbine analogs at central a-adrenoceptors

Structure affinity relationships for yohimbine analogs at central a-adrenoceptors. Baldwin, John J.; Huff, Joel R.; Randall, William C.; Vacca, Joseph P.; Zrada, Matthew M. (Merck Sharp and Dohme Res. Lab., West Point, PA 19486, USA). Eur. J. Med. Chem.--Chim. Ther., 20(1), 67-9 (English) 1985. CODEN: EJMCA5. ISSN: 0223-5234. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 9 Comparison of yohimbine (I) [146-48-5], rauwolscine [131-03-3], corynanthine [483-10-3], apoyohimbine [2671-50-3], and synthetic analogs of I was carried out at a1- and a2-adrenoceptors of calf cerebral cortex using radioligand binding techniques. These studies focused on the structural parameters which were believed to be important for affinity and selectivity. The role of the C-16 carbomethoxy substituent in detg. a1/a2-selectivity was confirmed and a pos. interaction of electronic origin between the group and the a2-adrenoceptor is suggested. The hydroxyl substituent at C-17 also made a major, but previously unrecognized, contribution to the selectivity of I-like mols. at these receptor subtypes.