Cardiovascular and locomotor effects of binary mixtures of common 'bath salts' constituents: Studies with methylone, methylenedioxypyrovalerone and caffeine in rats.

Background And Purpose: The use of 'bath salts' drug preparations has been associated with high rates of toxicity and death. Preparations often contain mixtures of drugs, including multiple synthetic cathinones or synthetic cathinones and caffeine. Little is known about the interactions of 'bath salts' constituents and adverse effects often reported by users.

Experimental Approach: This study used adult male Sprague-Dawley rats to characterise the cardiovascular effects, locomotor effects and pharmacokinetics of methylone, methylenedioxypyrovalerone (MDPV) and caffeine, administered alone and as binary mixtures. Dose-addition analyses were used to determine the effect levels of a strictly additive interaction for dose pairs.

Key Results: Methylone, MDPV and caffeine increased heart rate (HR) and locomotion, with methylone producing the largest increase in HR, MDPV producing the largest increase in locomotor activity and caffeine being the least effective in stimulating HR and locomotor activity. MDPV and caffeine increased mean arterial pressure (MAP), with caffeine being more effective than MDPV. The nature of the interactions between methylone and MDPV tended towards sub-additivity for all endpoints, whereas interactions between MDPV or methylone and caffeine tended to be additive or sub-additive for cardiovascular endpoints, and additive or supra-additive for increases in locomotion. No pharmacokinetic interactions were observed between individual constituents, but methylone appeared to display nonlinear pharmacokinetics at the largest dose evaluated.

Conclusion And Implications: These findings demonstrate that 'bath salts' preparations can impact both cardiovascular and locomotor effects and suggest that interactions among constituent drugs could contribute to the 'bath salts' toxidrome reported by human users.