E-5842 (Laboratories Dr Esteve).
Esteve is developing E-5842, a sigma1 opioid receptor ligand, as a potential therapy for psychosis. It has completed phase I trials [344879,346244]. As of May 1999, the site and protocol for phase II schizophrenia trials in the UK had been finalized and these were scheduled to begin shortly thereafter, with results likely to be available by the end of 2000 [365516]. E-5842 acted as an atypical antipsychotic in preclinical neurochemical and behavioral tests. Both acute (40 mg/kg ip for 2 h) and chronic (20 mg/kg ip daily for 21 days) administration of E-5842 increased PLC activity and the drug may thus achieve its antipsychotic effects via a signalling pathway involving phosphoinositide second messengers [336324]. E-5842 has a K(i) value of 4 nM at the sigma receptor [306875]. It blocks apomorphine-induced climbing, and antagonizes amphetamine-induced locomotor activity in mice [271405].
Beckett
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Neuroscience & Pharmacology Group, School of Biomedical Sciences, Faculty of Medicine & Health Sciences, Queens Medical Centre, Nottingham University, Nottingham, UK. Simon.Beckett@nottingham.ac.uk