2011-04-12·The Journal of pharmacy and pharmacology3区 · 医学
The preparation and properties of (+)- and (−)-guanoxan
3区 · 医学
Article
作者: Stafford, Anne ; Breimers, D. D. ; Stenlake, John B. ; Bowman, William C. ; Smail, Gordon A.
Abstract:
(±)-2-Aminomethyl-1, 4-benzodioxan has been resolved into its optically active isomers: (+)- and (-)-guanoxan have been synthesized from these. The pharmacological effects of racemic-guanoxan and of the two optical isomers have been compared on the isolated central ear artery of the rabbit, on the pithed rat in which pressor responses were evoked by stimulation of the thoraco-lumbar sympathetic outflow, and on the pre- and post-ganglionically stimulated nictitating membrane of the cat. The two isomers were equipotent in producing adrenergic neuron blockade. Initial catecholamine release was weak in the cat, but occurred more powerfully in the rabbit ear artery and in the rat. Ability to produce this effect resided mainly with the (+)-isomer. α-Adrenoreceptor blocking activity was detectable in the rat and was produced mainly by the (+)-isomer suggesting that its stereochemical configuration corresponds to that of D-(-)-noradrenaline. Ganglion blockade was an unimportant action of the compounds, but both isomers possessed weak atropine-like activity in the rat.
2011-04-12·The Journal of pharmacy and pharmacology3区 · 医学
Genetic evidence for the involvement of different oxidative mechanisms in drug oxidation
3区 · 医学
Article
作者: Wakile, L A ; Idle, J R ; Smith, R L ; Sloan, T P
Among adult male humans, phenotypically extensive metabolizers and phenotypically poor metabolizers of debrisoquine [1131-64-2] both metabolized 14C-labeled acetanilide [103-84-4] (500 mg, orally) to paracetamol-14C to the extent of 90% and at a rate of 0.13-0.14/h.Thus, the genetic defect in debrisoquine, guanoxan, and phenacetin oxidation, seen in 5% of the population, does not extend to acetanilide hydroxylation, indicating mediation by a different enzyme system and gene complex.
2011-04-12·The Journal of pharmacy and pharmacology3区 · 医学
Effects of guanoxan on intestinal smooth muscles
3区 · 医学
Article
作者: Bueno, J R ; Sollero, L ; de Castro, N J Nogueira
I.v. administration of guanoxan (I) to dogs anesthetized with pentobarbitone Na produced an immediate and long-lasting intestinal contraction concomitantly with hypotension.I (2 μg./ml. bathing fluid) induced contractions of the isolated guinea pig ileum in Tyrode solution; repeated administration did not induce tachyphylaxis and a dose-response relation was observed between 20-50 μg./ml. concentrationsThe ileal contractions were not blocked by the antihistamine drug, promethazine (0.5 μg./ml.), or the ganglionic blocking drug, hexamethonium (8 μg./ml.).Contractions induced by I (1 μg./ml.) on the isolated rabbit duodenum in Tyrode solution were not blocked by atropine sulfate (2 μg./ml.) or hexamethonium (8 μg./ml.).These seems to be a direct action of I on smooth muscle fibers.