Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats

Eur J Pharmacol. 2003 Feb 14;461(2-3):119-28. doi: 10.1016/s0014-2999(03)01313-x.


Our studies examined pharmacokinetic mechanisms involved in high-affinity (K(d) approximately 11 nM) monoclonal antibody-based antagonism of (+)-methamphetamine-induced locomotor effects. Male rats received (+)-methamphetamine (0.3, 1, or 3 mg/kg i.v.) followed 30 min later by saline or anti-(+)-methamphetamine monoclonal antibody. All groups received a constant dose of monoclonal antibody that was equimolar in binding sites to the body burden of a 1 mg/kg i.v. (+)-methamphetamine dose 30 min after administration. The monoclonal antibody antagonized locomotor effects due to 0.3 and 1 mg/kg (+)-methamphetamine. In contrast, monoclonal antibody treatment increased locomotor activity due to 3 mg/kg (+)-methamphetamine. We also investigated the serum and brain pharmacokinetics of (+)-methamphetamine without and with the monoclonal antibody. Rats received (+)-methamphetamine (1 mg/kg i.v.) followed by saline or monoclonal antibody treatment at 30 min. The monoclonal antibody significantly increased serum methamphetamine concentrations and significantly decreased brain methamphetamine concentrations. These data indicate that anti-(+)-methamphetamine monoclonal antibody-induced pharmacodynamics are complex, but are related to time-dependent changes in (+)-methamphetamine brain distribution.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphetamine / blood
  • Amphetamine / pharmacokinetics
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / pharmacology
  • Antibody Specificity
  • Area Under Curve
  • Brain / metabolism
  • Central Nervous System Stimulants / blood
  • Central Nervous System Stimulants / pharmacokinetics
  • Central Nervous System Stimulants / pharmacology*
  • Female
  • Male
  • Methamphetamine / immunology
  • Methamphetamine / pharmacokinetics
  • Methamphetamine / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tissue Distribution


  • Antibodies, Monoclonal
  • Central Nervous System Stimulants
  • Methamphetamine
  • Amphetamine