Orally Active Opioid Compounds from a Non-Poppy Source

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• 作者：Robert B. Raffa ; Jaclyn R. Beckett ; Vivek N. Brahmbhatt ; Theresa M. Ebinger ; Chrisjon A. Fabian ; Justin R. Nixon ; Steven T. Orlando ; Chintan A. Rana ; Ali H. Tejani ; Robert J. Tomazic
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：June 27, 2013
• 年：2013
• 卷：56
• 期：12
• 页码：4840-4848
• 全文大小：396K
• 年卷期：v.56,no.12(June 27, 2013)
• ISSN：1520-4804

文摘

The basic science and clinical use of morphine and other 鈥渙pioid鈥?drugs are based almost exclusively on the extracts or analogues of compounds isolated from a single source, the opium poppy (Papaver somniferum). However, it now appears that biological diversity has evolved an alternative source. Specifically, at least two alkaloids isolated from the plant Mitragyna speciosa, mitragynine ((E)-2-[(2S,3S)-3-ethyl-8-methoxy-1,2,3,4,6,7,12,12b-octahydroindolo[3,2-h]quinolizin-2-yl]-3-methoxyprop-2-enoic acid methyl ester; 9-methoxy coryantheidine; MG) and 7-hydroxymitragynine (7-OH-MG), and several synthetic analogues of these natural products display centrally mediated (supraspinal and spinal) antinociceptive (analgesic) activity in various pain models. Several characteristics of these compounds suggest a classic 鈥渙pioid鈥?mechanism of action: nanomolar affinity for opioid receptors, competitive interaction with the opioid receptor antagonist naloxone, and two-way analgesic cross-tolerance with morphine. However, other characteristics of the compounds suggest novelty, particularly chemical structure and possible greater separation from side effects. We review the chemical and pharmacological properties of these compounds.