Zuarth Gonzalez Julio D, Ragsdale Alexandria K, Mukhopadhyay Sushobhan, McCurdy Christopher R, McMahon Lance R, Obeng Samuel, Wilkerson Jenny L
Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX.
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL.
bioRxiv. 2025 May 21:2025.05.16.654392. doi: 10.1101/2025.05.16.654392.
The use of kratom as an alternative to conventional opioids has surged, driven largely by anecdotal reports of its efficacy for pain relief and opioid withdrawal management. The growing prevalence of kratom products enriched with 7-hydroxymitragynine (7-HMG), an active metabolite of mitragynine (MG), necessitates evaluating the respiratory effects of these alkaloids and determining if naloxone reverses their potential respiratory depressant effects. Respiratory parameters were measured in awake, freely moving female and male Sprague-Dawley rats using whole body plethysmography. To minimize handling-induced artifacts and ensure precise respiratory recordings, drugs were administered intravenously. Morphine and 7-HMG induced significant respiratory depression, evidenced by reductions in breathing frequency, tidal volume, and minute volume. In contrast, MG administration unexpectedly increased respiratory frequency. Naloxone fully reversed the respiratory depression induced by both morphine and 7-HMG but did not alter the respiratory stimulant effects produced by MG. These findings demonstrate that 7-HMG exhibits significant respiratory depressant properties similar to classical opioids, and importantly, such depressant effects are effectively antagonized by naloxone. Conversely, MG exerts respiratory stimulant effects through mechanisms independent of opioid receptor pathways. Collectively, these data highlight crucial pharmacological distinctions between kratom alkaloids, underscoring the risk associated with high 7-HMG-containing kratom products and suggesting that the predominant alkaloid MG may offer a safer respiratory profile.
由于有传闻称其在缓解疼痛和管理阿片类药物戒断方面有效， kratom作为传统阿片类药物替代品的使用激增。富含7-羟基帽柱木碱（7-HMG）（帽柱木碱（MG）的一种活性代谢物）的kratom产品日益普遍，因此有必要评估这些生物碱对呼吸的影响，并确定纳洛酮是否能逆转其潜在的呼吸抑制作用。使用全身体积描记法在清醒、自由活动的雌性和雄性Sprague-Dawley大鼠中测量呼吸参数。为了尽量减少处理引起的伪迹并确保精确的呼吸记录，药物通过静脉注射给药。吗啡和7-HMG诱导了显著的呼吸抑制，表现为呼吸频率、潮气量和分钟通气量降低。相比之下，给予MG意外地增加了呼吸频率。纳洛酮完全逆转了吗啡和7-HMG诱导的呼吸抑制，但并未改变MG产生的呼吸兴奋作用。这些发现表明，7-HMG表现出与经典阿片类药物相似的显著呼吸抑制特性，重要的是，这种抑制作用可被纳洛酮有效拮抗。相反，MG通过独立于阿片受体途径的机制发挥呼吸兴奋作用。总的来说，这些数据突出了kratom生物碱之间关键的药理学差异，强调了与高含量7-HMG的kratom产品相关的风险，并表明主要生物碱MG可能具有更安全的呼吸特征。
