Neuropharmacological studies in rodents on the action of RX 781094, a new selective alpha 2-adrenoceptor antagonist.
Several neuropharmacological effects of RX 781094, a new selective alpha 2-adrenoceptor antagonist, have been investigated in rodents. In rats, RX 781094 (0.1-1.0 mg kg-1, i.v.) produced a rapid dose-related reversal of cortical EEG synchronisation and behavioural sedation, induced by clonidine or the more selective alpha 2-adrenoceptor agonist, guanoxabenz. The alpha 2-adrenoceptor antagonists yohimbine and mianserin were also effective in blocking guanoxabenz-induced EEG synchronisation but had a lower potency than did RX 781094. In specificity experiments, RX 781094 (1.0 mg kg-1, i.v.) failed to antagonise the EEG synchronisation and pronounced behavioural sedation induced by the CNS depressant sodium pentobarbitone (15 mg kg-1, i.v.). In mice, pretreatment (i.v. or p.o.) with RX 781094 inhibited in a dose-dependent way both guanoxabenz-induced behavioural hypoactivity and clonidine-induced hypothermia. By itself, RX 781094 had no effect on the temperature of normal mice. In sleep-waking studies in rats, RX 781094 (0.1 and 1.0 mg kg-1, i.v.) had no measurable stimulant or depressant effect on the CNS, in contrast to (+)-amphetamine (1.0 mg kg-1, i.v.) which elicited marked CNS stimulation. These results support the conclusion that RX 781094 is a potent antagonist at central alpha 2-adrenoceptors.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology*; D004336:Drug Antagonism; D004569:Electroencephalography; D006143:Guanabenz / Q000031:analogs & derivatives / Q000494:pharmacology; D019329:Idazoxan; D008297:Male; D010296:Parietal Lobe / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012890:Sleep / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D004147:Dioxins; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D006143:Guanabenz; D003000:Clonidine; C028782:guanoxabenz; D019329:Idazoxan