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Monoclonal Antibodies as Pharmacokinetic Antagonists for the Treatment of (+)-Methamphetamine Addiction

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Developing specific medications to treat (+)-methamphetamine (METH) addiction is a difficult challenge because METH has multiple sites of action that are intertwined with normal neurological function. As a result, no small molecule medication for the treatment of METH addiction has made it through the FDA clinical trials process. With the invention of a new generation of proteinbased therapies, it is now possible to consider treating drug addiction by an entirely different approach. This new approach is based on the discovery of very high affinity anti-METH monoclonal antibodies (mAbs), which are non-addictive and antagonize METH effects from the blood stream without entering the brain. Due to a very long biological half-life, anti-METH mAbs would only need to be administered once every 2-4 weeks, aiding in patient compliance. As a relapse prevention medication, anti-METH mAbs could reduce or prevent the rewarding effects of a relapse to METH use and thereby improve a patient's probability of remaining in therapy and recovering from their addiction. In this review, we discuss the discovery process of anti-METH mAbs, with a focus on the preclinical development leading to high affinity anti-METH mAb antagonists.

Keywords: Addiction; Amphetamines; MAB6H4; METH; PCKN; cognitive behavioral therapy; monoclonal antibodies; pharmacokinetics; psychosis; rat; vaccines

Document Type: Research Article


Publication date: 2011-12-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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