N-[2-( m-methoxyphenyl)ethyl]- N-ethyl-2-(1-pyrrolidinyl)ethylamine (UMB 116) is a novel antagonist for cocaine-induced effects

• Published in: European journal of pharmacology Vol. 542; no. 1; pp. 61 - 68
• Main Authors: Daniels, AnTawan, Ayala, Erika, Chen, Weibin, Coop, Andrew, Matsumoto, Rae R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 07.08.2006; Elsevier
• Subjects: Animals; Anticonvulsants - chemistry; Anticonvulsants - metabolism; Anticonvulsants - pharmacology; Binding, Competitive - drug effects; Biological and medical sciences; Brain - metabolism; Cocaine; Cocaine - administration & dosage; Cocaine - toxicity; Convulsion; Dose-Response Relationship, Drug; Ethylamines - chemistry; Ethylamines - metabolism; Ethylamines - pharmacology; Haloperidol - pharmacology; Injections, Intraperitoneal; Locomotor activity; Male; Medical sciences; Mice; Motor Activity - drug effects; Pharmacology. Drug treatments; Pyrrolidines - chemistry; Pyrrolidines - metabolism; Pyrrolidines - pharmacology; Radioligand Assay; Receptors, sigma - metabolism; Seizures - chemically induced; Seizures - mortality; Seizures - prevention & control; Survival Rate; σ receptor; σ receptor; Cocaine; Convulsion; Locomotor activity; Nervous system diseases; CNS stimulant; Psychotropic; Sigma receptor; Pyrrolidine derivatives; Local anesthetic; Ester; Locomotion; Drug of abuse; Antagonist; Neurological disorder
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.03.062

Previous research has shown that σ receptors participate in the actions of cocaine in the body. This has led to investigations of the use of novel agents such as BD1008, BD1067 and YZ-011 as cocaine antagonists. In the present study, three novel analogs (UMB115, UMB116, UMB117), representing composites of these earlier compounds, were evaluated in receptor binding and behavioral studies. In the receptor binding studies, the compounds were shown to have high affinity for σ receptors and much lower affinities for non-σ sites. For the behavioral experiments, Swiss Webster mice were pre-treated with saline or one of the novel compounds (0.1–10 mg/kg), followed 15 min later by a convulsive (60 mg/kg), lethal (125 mg/kg), or locomotor stimulatory (10 mg/kg) dose of cocaine. The results showed that UMB115, UMB116 and UMB117 significantly ( P < 0.05) inhibited cocaine-induced convulsions when administered as a pre-treatment to cocaine. Cocaine-induced lethality was significantly attenuated by UMB116 ( P < 0.05), but not by UMB115 and UMB117. All three compounds significantly ( P < 0.05) altered the locomotor stimulatory effects of cocaine, with UMB115 and UMB116 exhibiting attenuating actions. Together, the studies suggest UMB116 as a novel cocaine antagonist.