Poison Control and Medical Forensic Chemistry Center, Jazan Health Affairs, Ministry of Health, Jazan, Saudi Arabia.
Department of Biochemistry, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia.
Drug Metab Pers Ther. 2023 Mar 9;38(2):199-207. doi: 10.1515/dmpt-2022-0154. eCollection 2023 Jun 1.
(Khat) is a stimulant plant that contains cathine and cathinone, which its abuses induce euphoria, alertness, and motor activity. Since the toxicokinetics of these substances remain unclear, this study was carried out to investigate the disposition kinetics of cathine and cathinone, the neurotransmitter profile, following a single dose of extract in rats.
Twenty-four adult male Wistar albino rats (250-300 g) were randomly selected and divided into six groups of four rats each. All groups received a single oral dose of 2,000 mg/kg body weight, and blood and tissue samples from the brain, lung, heart, liver, and kidney were obtained at intervals of 0.5, 1, 2.5, 5, 12, and 24 h. The cathine and cathinone concentrations were identified and quantified using ion trap ultra-high performance liquid chromatography (HPLC-IT/MS). The neurotransmitter profile was detected using the quadrupole time of flight UPLC-QTOF/MS method.
The lung, liver, and heart tissues attained the highest levels of cathine, while the highest level of cathinone was determined in the heart. Cathine and cathinone concentrations in the blood and heart peaked at 0.5 h. The concentrations peaked in the brain 2.5 h later, indicating that the heart had an immediate effect, whereas the brain had a longer-lasting one. They have longer half-lives (2.68 and 5.07 h, respectively) and may remain in the brain for longer durations (3.31 and 2.31 h, respectively). The neurotransmitters epinephrine, dopamine, norepinephrine, and serotonin were detected in a delayed, prolonged and organ-specific manner.
Cathine and cathinone were deposited in considerable concentrations in all tissues analyzed, with the highest C in the lung and T in the heart tissues but not in the brain. In addition, neurotransmitters such as adrenaline, dopamine, norepinephrine, and serotonin were differentially detected in all tested samples in a organ-specific fashion. More study is needed to identify cathine and cathinone's effects on neurotransmitter profiles. Nevertheless, these findings provided a further basis for experimental, clinical, and forensic investigations.
（阿拉伯茶）是一种含有卡西酮和去甲伪麻黄碱的兴奋剂植物，其滥用会引起欣快、警觉和运动活动。由于这些物质的毒代动力学仍不清楚，因此进行了这项研究，以调查大鼠单次服用 提取物后卡西酮和去甲伪麻黄碱的处置动力学、神经递质谱。
随机选择 24 只成年雄性 Wistar 白化大鼠（250-300g），并将其分为 6 组，每组 4 只。所有组均接受 2000mg/kg 体重的单次口服剂量，并在 0.5、1、2.5、5、12 和 24 小时间隔从大脑、肺、心脏、肝脏和肾脏获得血液和组织样本。使用离子阱超高液相色谱（HPLC-IT/MS）鉴定和定量卡西酮和去甲伪麻黄碱的浓度。使用四极杆飞行时间 UPLC-QTOF/MS 方法检测神经递质谱。
肺、肝和心脏组织中卡西酮浓度最高，而心脏组织中去甲伪麻黄碱浓度最高。血液和心脏中的卡西酮和去甲伪麻黄碱浓度在 0.5 小时时达到峰值。大脑中的浓度在 2.5 小时后达到峰值，这表明心脏具有即时效应，而大脑具有更长的作用时间。它们具有较长的半衰期（分别为 2.68 和 5.07 小时），并且可能在大脑中停留更长时间（分别为 3.31 和 2.31 小时）。以延迟、延长和器官特异性的方式检测到去甲肾上腺素、多巴胺、去甲肾上腺素和 5-羟色胺等神经递质。
卡西酮和去甲伪麻黄碱在分析的所有组织中都以相当高的浓度沉积，肺中的 C 最高，心脏组织中的 T 最高，但不在大脑中。此外，以器官特异性方式在所有测试样本中以不同的方式检测到肾上腺素、多巴胺、去甲肾上腺素和 5-羟色胺等神经递质。需要进一步研究以确定卡西酮和去甲伪麻黄碱对神经递质谱的影响。尽管如此，这些发现为实验、临床和法医学研究提供了进一步的依据。
