Seaman Robert W, Galindo David G, Stinson Benjamin T, Sulima Agnieszka, Rice Kenner C, Javors Martin A, Ginsburg Brett C, Collins Gregory T
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Br J Pharmacol. 2025 Apr;182(8):1836-1855. doi: 10.1111/bph.17444. Epub 2025 Jan 22.
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.
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.
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.
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.
“浴盐”类药物制剂的使用与高毒性和高死亡率相关。这些制剂通常含有多种药物混合物，包括多种合成卡西酮或合成卡西酮与咖啡因。对于“浴盐”成分之间的相互作用以及使用者经常报告的不良反应知之甚少。
本研究使用成年雄性斯普拉格-道利大鼠来表征单独给药以及以二元混合物形式给药时，甲酮、亚甲基二氧吡咯戊酮（MDPV）和咖啡因对心血管的影响、运动效应和药代动力学。采用剂量相加分析来确定剂量对的严格相加相互作用的效应水平。
甲酮、MDPV和咖啡因均可提高心率（HR）和运动能力，其中甲酮使HR升高幅度最大，MDPV使运动活性升高幅度最大，而咖啡因刺激HR和运动活性的效果最差。MDPV和咖啡因可提高平均动脉压（MAP），其中咖啡因的效果比MDPV更显著。对于所有终点指标，甲酮与MDPV之间的相互作用性质倾向于次相加性，而MDPV或甲酮与咖啡因之间的相互作用在心血管终点指标方面倾向于相加或次相加性，在运动增加方面倾向于相加或超相加性。未观察到各成分之间存在药代动力学相互作用，但在评估的最大剂量下，甲酮似乎呈现非线性药代动力学。
这些发现表明，“浴盐”制剂可影响心血管和运动效应，并提示成分药物之间的相互作用可能导致人类使用者报告的“浴盐”中毒综合征。
