Effects of two venotropic drugs on inactivation and O-methylation of catecholamines in an isolated canine vein.
Clobenoside (1-O-ethyl-3-O-propyl-5,6-di-O-chlorbenzyl-D-glucofuranose, CL) and Venoruton [O-(beta-hydroxyethyl)-rutosides, HR] did not cause supersensitivity to either exogenous or endogenous (stimulation-released) noradrenaline, in strips of the saphenous vein of the dog. Both drugs caused a significant blockade of the inactivation of noradrenaline, in oil immersion experiments. In incubation experiments with 3H-isoprenaline, CL and HR (100 to 900 mumol/l) caused a dose-dependent inhibition of O-methylation; they had additive effects with the COMT inhibitor, U-0521 and their effects were abolished in the presence of hydrocortisone. In incubation experiments with 3H-adrenaline, formation of metanephrine was inhibited, neuronal uptake and oxidative deamination remaining unaffected. After intravenous administration of HR (100 mg/kg), the O-methylating capacity of blood vessels was similarly reduced. It is concluded that CL and HR affected exclusively the extraneuronal O-methylating system (probably both by inhibiting COMT and depressing uptake) and that this effect may contribute to their therapeutic actions.
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines / Q000378:metabolism*; D004285:Dogs; D004558:Electric Stimulation; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism; D008745:Methylation; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D012431:Rutin / Q000031:analogs & derivatives*; D012501:Saphenous Vein / Q000187:drug effects
D000925:Anticoagulants; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D006896:Hydroxyethylrutoside; D012431:Rutin; C005865:troxerutin; C044699:clobenoside; D005947:Glucose; D007545:Isoproterenol; D009638:Norepinephrine