In vivo pharmacological activity of r 47 243 in rat: A comparison with putative α₂‐adrenoceptor antagonists

Abstract

The study examined the effects of R 47 243 and its (-)-and (+)-isomers as well as those of the putative a2-antagonists yohimbine, piperoxan, CGS 7225 A, and idazoxan at 1-to 24-hr time intervals after oral administration in rats. The experiments determined the antagonism produced by these compounds of the loss of the righting reflex (LRR) and of the exophthalmia (EXO) induced by intraperitoneal injection of 20 mg/kg of xylazine. Antagonism of LRR constitutes an in vivo measure of drug antagonist effects at CNS receptors that mediate behavioral depression produced by putative a2-agonists; antagonism of EX0 offers an in vivo measure of a,-antagonist activity. More so than idazoxan or any of the other putative a2-antagonists tested, R 47 243 appeared to be a potent, long acting, and specific antagonist; it also acted as a full antagonist rather than as a partial agonist and showed excellent oral absorption.

Reduced MPTP toxicity in noradrenaline transporter knockout mice

“…2001; Archer and Fredriksson 2003). In addition, treatment with alpha 2 antagonists can reduce PD symptoms such as dyskinesia and reverse PD symptoms in monkeys (Colpaert and Raeymaekers 1986; Colosimo and Craus 2003). In previous studies, alpha 2 antagonists have been shown to be neuroprotective for striatal neurons against quinolinic acid lesion and methamphetamine toxicity (Fornai et al .…”

“…For example, alpha 2 agonists and antagonists can potentiate the anti-hypokinetic effects of L-dopa in PD patients and animal models of the disease (Serrano-Duenas 2000; Rascol et al 2001;Archer and Fredriksson 2003). In addition, treatment with alpha 2 antagonists can reduce PD symptoms such as dyskinesia and reverse PD symptoms in monkeys (Colpaert and Raeymaekers 1986;Colosimo and Craus 2003). In previous studies, alpha 2 antagonists have been shown to be neuroprotective for striatal neurons against quinolinic acid lesion and methamphetamine toxicity (Fornai et al 1998;Martel et al 1998).…”