Role of endogenous catecholamines in the anti-inflammatory activity of alpha-adrenoceptor blocking agents.
1 Drugs which release or modify the response to catecholamines were examined for their effect on the permeability of the mouse peritoneal vascular bed to circulating plasma albumin, labelled with Evans blue.2 Phenoxybenzamine, phentolamine, piperoxane, yohimbine or cocaine reduced the extravasation of Evans blue into the peritoneum, an effect which was antagonized by beta-adrenoceptor blocking drugs. The inhibitory effect of desipramine on the extravasation of Evans blue was less completely antagonized by beta-adrenoceptor blockade.3 Inhibition of catecholamine biosynthesis, ganglion blockade or adrenergic neurone blockade antagonized the reduction in dye extravasation by alpha-adrenoceptor blocking agents and cocaine, but had no significant effect on the response to desipramine. The inhibitory effects of alpha-adrenoceptor blocking agents on dye extravasation were not prevented by bilateral adrenalectomy.4 Mice subjected to the procedure for estimation of vascular permeability excreted increased amounts of adrenaline and noradrenaline. Pretreatment with phenoxybenzamine, piperoxane or cocaine further increased catecholamine excretion, but desipramine caused only a small increase in catecholamine excretion which did not correlate with its effect on dye extravasation.5 It is suggested that phenoxybenzamine, phentolamine, piperoxane and cocaine reduce vascular permeability in the mouse peritoneum by releasing and/or potentiating the effects of endogenous catecholamines on beta-adrenoceptors. Endogenous catecholamines do not appear to be involved in the anti-inflammatory activity of desipramine.
D000311:Adrenal Glands / Q000502:physiology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002395:Catecholamines / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology / Q000652:urine; D005260:Female; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology / Q000652:urine; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D014599:Uterus / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000893:Anti-Inflammatory Agents; D002395:Catecholamines; D004147:Dioxins; D008781:Methyltyrosines; D010880:Piperidines; D012709:Serum Albumin; D010643:Phenoxybenzamine; D015016:Yohimbine; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine