Mouse anti-MDPV monoclonal antibody, clone IN568

This article presents information on the predominant synthetic cathinones used in the Western world, mephedrone and methylenedioxypyrovalerone (MDPV). Synthetic cathinones are commonly used drugs of abuse in the United States and Europe, with numerous cases of patient harm and death. Patients exhibit many neurological, cardiovascular, and muscular adverse events and frequently require therapy to control psychotic or agitated states and acute kidney injury resulting from myopathy or rhabdomyolysis. There are potential genetic polymorphisms and drug interactions that might accentuate risk, but there are no studies evaluating to what extent this occurs or if it is clinically relevant. Clinicians should be aware of the known pharmacology, pharmacokinetics, and reports of effects to detect potential issues and treat patients presenting with these adverse effects.

The broad diversity of synthetic cathinone psychostimulant drugs that are available to users complicates research efforts to provide understanding of health risks. Second generation cathinones pentedrone and pentylone are distinguished from each other by the 3,4-methylenedioxy structural motif (which distinguishes methamphetamine from 3,4-methylenedioxymethamphetamine) and each incorporates the a-alkyl chain motif contained in the transporter-inhibitor cathinones (3,4-methylenedioxypyrovalerone (MDPV), alpha-pyrrolidinopentiophenone (alpha-PVP)) but not in the monoamine releasers (mephedrone, methylone). Studies were conducted in male and female Wistar rats to compare locomotor and thermoregulatory effects of pentedrone, pentylone and methylone using an implanted radiotelemetry system. Reinforcing effects were assessed in female Wistar rats trained in the intravenous selfadministration (IVSA) procedure and subjected to dose-substitution (0.025-0.3 m/gkg/inf) under a fixed-ratio 1 response contingency. Pentedrone, pentylone and methylone dose-effect curves were contrasted with those for alpha-PVP and alpha-pyrrohdmohexiophenone (alpha-PHP). Dose dependent increases in locomotion were observed after intraperitoneal injection of pentylone (0.5-10.0 mg/kg), pentedrone (0.5 -10.0 mg/kg) or mephedrone (0.5-10.0 mg/kg) in male and female rats. The maximum locomotor effect was similar across drugs but lasted longest after pentedrone. Mean body temperature did not vary systematically more than 0.5 degrees C after pentedrone or pentylone in either sex. A sustained hyperthermia (0.4-0.8 degrees C) was observed for four hours after 10.0 mg/kg methylone in male rats. More infusions of pentedrone or pentylone were self-administered compared with methylone, but all three were less potent than alpha-PVP or alpha-PHP. These studies support the inference that second generation cathinones pentylone and pentedrone have abuse liability greater than that of methylone. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'