Despite the widespread use of bath salts, there is a paucity of information about their pharmacology. Using assay methods in rat brain synaptosomes, it has been shown that mephedrone and methylone act as substrates at plasma membrane transporters for norepinephrine, dopamine, and serotonin, thereby stimulating non-exocytotic release of these neurotransmitters (Baumann et al, 2012). Mephedrone is about two-times more potent than methylone as a transporter substrate. In vivo microdialysis studies in rats confirm that mephedrone and methylone (0.3 or 1.0 mg/kg, i.v.) increase extracellular levels of dopamine and serotonin in the brain, similar to the effects of MDMA. Little is known about the pharmacology of MDPV, but our unpublished findings show the drug is a potent blocker of dopamine and norepinephrine uptake. The fact that synthetic cathinones enhance dopamine transmission predicts high abuse liability. Hadlock et al (2011) reported that i.v. mephedrone (0.24 mg/infusion) is readily self-administered by rats, but reinforcing effects of other synthetic cathinones are largely unexplored. Few preclinical studies have examined the pharmacokinetics and metabolism of synthetic cathinones or the consequences of chronic drug dosing, and these types of investigations are needed.

Serotonin transporter substrates like MDMA are known to produce sustained deficits in brain serotonin neurons of laboratory animals, so mephedrone and methylone could have similar actions. Repeated subcutaneous (s.c.) administration of either drug to single-housed rats (3 or 10 mg/kg, three doses) has no long-lasting effects on brain tissue monoamines (Baumann et al, 2012), but administration of higher doses of mephedrone to group-housed rats (10 or 25 mg/kg, s.c., four doses) causes selective depletion of brain serotonin (Hadlock et al, 2011). It is noteworthy that MDPV is the chief substance detected in blood and urine from patients hospitalized for bath salts overdose in the US (Spiller et al, 2011). Such patients display agitation, combative behavior, hallucinations, delusions, hyperthermia, tachycardia and hypertension (Prosser and Nelson, 2012; Spiller et al, 2011). Health care workers should be aware that patients presenting with this constellation of symptoms may have taken bath salts, and appropriate supportive care should be provided. Owing to the increasing availability of ‘replacement’ cathinones with unknown pharmacology (Shanks et al, 2012), it seems likely that emergency departments will continue to encounter patients suffering from adverse effects of synthetic cathinone abuse.

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