Abstract:
Ibogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state, which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to noribogaine, which also shows antiaddictive effects but with a distinct pharmacological profile, making this drug a promising therapeutic candidate. Therefore, we still ignore whether the sleep/wake alterations depend on ibogaine or its principal metabolite noribogaine. To answer this question, we conducted polysomnographic recordings in rats following the administration of pure noribogaine. Our results show that noribogaine promotes wakefulness while reducing slow-wave sleep and blocking REM sleep, similar to our previous results reported for ibogaine administration. Thus, we shed new evidence on the mechanisms by which iboga alkaloids work in the brain.
摘要:
Ibogaine是一种有效的非典型迷幻药,由于其在临床前和临床研究中具有抗成瘾和抗抑郁作用,因此引起了广泛关注。我们小组先前的研究表明,伊博加因抑制睡眠并产生改变的觉醒状态,这类似于自然的REM睡眠。然而,全身给药后,伊博加因被迅速代谢为去利博加因,它也显示出抗成瘾作用,但具有独特的药理学特征,使这种药物成为有前途的治疗候选药物。因此,我们仍然忽略睡眠/觉醒改变是否取决于伊博加因或其主要代谢产物noribogaine。为了回答这个问题,我们在使用纯去利博加因后对大鼠进行了多导睡眠图记录。我们的结果表明,去利波加因促进觉醒,同时减少慢波睡眠和阻断REM睡眠,与我们之前报道的伊博加因给药结果相似.因此,我们为iboga生物碱在大脑中的作用机制提供了新的证据。