Pharmacokinetic antagonism of (+)-methamphetamine discrimination by a low-affinity monoclonal anti-methamphetamine antibody.
Animals were trained to discriminate 5 or 10 mg/kg cocaine (rats), or 3 mg/kg (+)-amphetamine (pigeons) from saline, after which dose-response curves were determined for (+)-methamphetamine and other drugs before and after administration of a (+)-methamphetamine-specific monoclonal antibody (K(D) =250 nM). In rats trained to discriminate 10 mg/kg cocaine from saline, intravenous (+)-methamphetamine was about three times more potent as a discriminative stimulus than intraperitoneal (+)-methamphetamine. Also in these rats, intraperitoneal (+)-methamphetamine and (+)-amphetamine were about equipotent as discriminative stimuli, and were about three times more potent than intraperitoneal cocaine. In pigeons trained to discriminate 3 mg/kg intramuscular (i.m.) (+)-amphetamine from saline, (+)-methamphetamine and (+)-amphetamine were nearly equipotent, while cocaine was slightly less potent. In rats trained to discriminate 5 or 10 mg/kg cocaine from saline, intravenous administration of 1 g/kg of the antibody shifted both intravenous and intraperitoneal dose-response curves for (+)-methamphetamine discrimination approximately threefold to the right at 1 or 4 days after administration of the antibody. In pigeons trained to discriminate 3 mg/kg intramuscular (+)-amphetamine from saline, a similar shift of the (+)-methamphetamine dose-response curve to the right also lasted for 4-7 days. However, the antibody did not affect the (+)-amphetamine dose-response curve (pigeons), or the cocaine (rats) dose-response curve. The data show that a low affinity anti-(+)-methamphetamine-specific antibody can produce a specific antagonism of an effect of (+)-methamphetamine that is closely associated with its abuse.
McMillan
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Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, 72205, USA. McMillanDonaldE@uams.edu
Hardwick
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Li
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Owens
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D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000493:pharmacokinetics*; D010856:Columbidae; D003463:Cues; D004192:Discrimination, Psychological; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000697:Central Nervous System Stimulants; D008694:Methamphetamine