Abstract：
OBJECTIVE: Demand for new antidepressants has resulted in a re-evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin-containing \"magic\" mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects.
METHODS: We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood-brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound.
RESULTS: In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood-brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5-HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5-HT2A-mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles.
CONCLUSIONS: Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations.
METHODS: We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood-brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound.
RESULTS: In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood-brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5-HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5-HT2A-mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles.
CONCLUSIONS: Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations.
摘要：
目的：对新抗抑郁药的需求导致了对迷幻药治疗潜力的重新评估。在含有psilocybin的“魔术”蘑菇中发现的几种色胺与psilocybin具有化学相似性。早期工作表明，它们可能共享生物靶标。然而,很少有研究探索它们的药理和行为作用。
方法：我们比较了囊藻毒素，norbaeocystin和aeruginascin与psilocybin，以确定它们是否被相同的酶代谢，同样穿透血脑屏障，作为类似受体的配体，并类似地调节啮齿动物的行为。我们还评估了每种化合物的稳定性和最佳储存和处理条件。
结果：体外酶动力学测定发现，所有化合物通过碱性磷酸酶和单胺氧化酶代谢的去磷酸化率几乎相同。Further,我们发现，只有baeocystin和norbaeocystin的去磷酸化产物穿过血脑屏障模拟物的程度与psilocybin的去磷酸化形式相似，psilocin.在体外细胞成像测定中，发现去甲霉素的去磷酸化形式激活5-HT2A受体，其功效与psilocin和norpsilocin相似。行为上,只有psilocybin在大鼠中引起头部抽搐反应，5-HT2A介导的迷幻作用和致幻潜能的标志物。然而,像psilocybin，norbaeocystin改善了强迫游泳试验的结果。所有化合物对肾脏和肝脏健康指标的影响最小，建议无害的安全概况。
结论：总的来说，这项工作表明其他天然存在的色胺，尤其是去位素,可能与psilocybin共享重叠的治疗潜力，但不会引起幻觉.
方法：我们比较了囊藻毒素，norbaeocystin和aeruginascin与psilocybin，以确定它们是否被相同的酶代谢，同样穿透血脑屏障，作为类似受体的配体，并类似地调节啮齿动物的行为。我们还评估了每种化合物的稳定性和最佳储存和处理条件。
结果：体外酶动力学测定发现，所有化合物通过碱性磷酸酶和单胺氧化酶代谢的去磷酸化率几乎相同。Further,我们发现，只有baeocystin和norbaeocystin的去磷酸化产物穿过血脑屏障模拟物的程度与psilocybin的去磷酸化形式相似，psilocin.在体外细胞成像测定中，发现去甲霉素的去磷酸化形式激活5-HT2A受体，其功效与psilocin和norpsilocin相似。行为上,只有psilocybin在大鼠中引起头部抽搐反应，5-HT2A介导的迷幻作用和致幻潜能的标志物。然而,像psilocybin，norbaeocystin改善了强迫游泳试验的结果。所有化合物对肾脏和肝脏健康指标的影响最小，建议无害的安全概况。
结论：总的来说，这项工作表明其他天然存在的色胺，尤其是去位素,可能与psilocybin共享重叠的治疗潜力，但不会引起幻觉.
