ABSTRACT
Methylenedioxypyrovalerone (MDPV) is a synthetic, cathinone-derivative, central nervous system stimulant taken to produce a cocaine- or methamphetamine-like high. Physical manifestations include tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, hyperkalaemia, disseminated intravascular coagulation, oliguria and seizures. We report a patient who presented with severe metabolic acidosis, multi-organ dysfunction, rhabdomyolysis, hyperkalaemia and seizures. This case highlights that even though a urine drug screen for routine psychostimulant drugs is negative, clinicians need to be vigilant about the adverse effects of MDPV as a possible cause of multi-organ dysfunction. Substances such as this can only be detected by special tests, such as gas/liquid chromatography mass spectrometry. This is the first reported case of MDPV toxicity successfully treated in Australia to the best of our knowledge.
Subject(s)
Benzodioxoles/poisoning , Central Nervous System Stimulants/poisoning , Designer Drugs/poisoning , Multiple Organ Failure/chemically induced , Multiple Organ Failure/therapy , Pyrrolidines/poisoning , Adult , Alkaloids/agonists , Australia , Fever/chemically induced , Gas Chromatography-Mass Spectrometry , Humans , Male , Renal Replacement Therapy , Rhabdomyolysis/chemically induced , Synthetic CathinoneABSTRACT
Cytisine very potently binds and activates the alpha 3 beta 4 and alpha 7 nicotinic subtypes, but only partially agonises the alpha 4 beta 2 subtype. Although with a lower affinity than cytisine, new cytisine derivatives with different substituents on the basic nitrogen (CC1-CC8) bind to both the heteromeric and homomeric subtypes, with higher affinity for brain [3H]epibatidine receptors. The cytisine derivatives were tested on the Ca(2+) flux of native or transfected cell lines expressing the rat alpha 7, or human alpha 3 beta 4 or alpha 4 beta 2 subtypes using Ca(2+) dynamics in conjunction with a fluorescent image plate reader. None elicited any response at doses of up to 30-100 microM, but all inhibited agonist-induced responses. Compounds CC5 and CC7 were also electrophysiologically tested on oocyte-expressed rat alpha 4 beta 2, alpha 3 beta 4 and alpha 7 subtypes. CC5 competitively antagonised the alpha 4 beta 2 and alpha 3 beta 4 subtypes with similar potency, whereas CC7 only partially agonised them with maximum responses of respectively 3% and 11% of those of 1 mM acetylcholine. Neither compound induced any current in the oocyte-expressed alpha 7 subtype, and both weakly inhibited acetylcholine-induced currents. Adding chemical groups of a different class or size to the basic nitrogen of cytisine leads to compounds that lose full agonist activity on the alpha 3 beta 4 and alpha 7 subtypes.
