PT  - JOURNAL ARTICLE
AU  - D. E. McMillan
AU  - W. C. Hardwick
AU  - M. Li
AU  - M. G. Gunnell
AU  - F. I. Carroll
AU  - P. Abraham
AU  - S. M. Owens
TI  - Effects of Murine-Derived Anti-Methamphetamine Monoclonal Antibodies on (+)-Methamphetamine Self-Administration in the Rat
AID  - 10.1124/jpet.103.061762
DP  - 2004 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1248--1255
VI  - 309
IP  - 3
4099  - http://jpet.aspetjournals.org/content/309/3/1248.short
4100  - http://jpet.aspetjournals.org/content/309/3/1248.full
SO  - J Pharmacol Exp Ther2004 Jun 01; 309
AB  - Two murine-derived anti-methamphetamine monoclonal antibodies were studied as potential pharmacokinetic antagonists of (+)-methamphetamine self-administration by rats. Intravenous administration of a 1 g/kg dose of the lower affinity [antibody equilibrium dissociation constant (Kd) = 250 nM] monoclonal antibody (mAb) designated mAb6H8, 1 day before the start of several daily 2-h self-administration sessions produced effects that depended on the dose of (+)-methamphetamine. mAb6H8 increased the rate of self-administration of a unit dose of 0.06 mg/kg (+)-methamphetamine, had little effect on the rate of self-administration of a unit dose of 0.03 mg/kg (+)methamphetamine, and lowered the rate of self-administration of a unit dose of 0.01 mg/kg (+)-methamphetamine to a level similar to that after saline substitution. mAb-induced changes in rates of self-administration occurred very early in self-administration sessions and lasted for 3 to 7 days. Intravenous administration of a 1 or a 0.6 g/kg dose of a higher affinity (Kd = 11 nM) mAb designated mAb6H4, 24 h before the first of several self-administration sessions, produced very similar effects to the lower affinity mAb, despite the more than 20-fold greater affinity for (+)-methamphetamine. It is proposed that these anti-methamphetamine antibodies bind some of the self-administered (+)-methamphetamine before it can penetrate into brain, thereby reducing the amount of free drug available to function as a reinforcer. Although neither of these mAb medications are optimal antibodies for treating (+)-methamphetamine abuse, the experiments demonstrate that anti-(+)-methamphetamine monoclonal antibodies can attenuate the self-administration of the drug and suggest the potential of using monoclonal antibodies as pharmacokinetic antagonists of (+)-methamphetamine. The American Society for Pharmacology and Experimental Therapeutics