Psychostimulant Abuse & HIV Infection: Cocaine, Methamphetamine & “Bath Salts” Cathinone Analogues

Psychostimulants are among the most widely-abused substances worldwide, and typically exert their abuse-related effects via interactions with monoamine reuptake transporters within the CNS. Over the last decade, a symbiotic relationship between psychostimulant abuse and HIV infection has been demonstrated, where psychostimulants potentiate the effects of HIV infection, and HIV infection increases sensitivity to psychostimulant drugs. Most recently, a new class of designer psychostimulants has emerged in abuse-ready “bath salt” preparations. These commercial products typically contain ring-substituted and/or side-chain-substituted analogues of cathinone, which is itself a psychostimulant drug of abuse in its natural plant form. The cathinone analogues exhibit a range of interactions with monoamine transporters, from cocaine-like reuptake inhibition to methamphetamine-like release. Since the primary mechanism of action of these novel drugs overlaps with those of traditional psychostimulants, it may be the case that the cathinone analogues also interact with HIV infection. As use of these emerging cathinone-derived drugs continues to rise, there is an urgent need to better understand the pharmacology and toxicology of these novel compounds, both in terms of their abuse-related effects, and in terms of their capacity to interact with HIV infection

Table 1

Interaction of psychostimulants with monoamine transporters

Affinity (shaded columns) is expressed as Ki values (µM), and stimulation of monoamine release (unshaded columns) is expressed as EC50 values (µM). In both cases, smaller numbers represent higher affinity and greater potency, respectively. Dashes indicate that a compound was inactive in that assay, while “N.T.” indicates that the compound was not tested. NET release data originally reported by Baumann et al., 2013. All other data originally reported by Simmler et al., 2013.

DRUG	DAT		NET		SERT
	Affinity	Release	Affinity	Release	Affinity	Release
Cocaine	0.28	> 100	4.47	--	1.10	> 100
Methamphetamine	1.85	1.56	4.28	N.T.	26.70	> 33
MDPV	0.01	> 100	0.08	--	2.86	> 100
Mephedrone	3.40	3.75	> 25	0.058	> 30	5.98
Methylone	2.73	> 100	> 25	0.140	> 30	> 10
Naphyrone	0.04	> 100	0.18	N.T.	0.18	> 100

Full article at:  http://ht.ly/SYDCr 

By: Brenda M. Gannon, Emily E. Reichard, and William E. Fantegrossi, Ph.D.

Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR

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