McKenna D J
Botanical Dimensions, Occidental, CA 95465, USA.
Behav Brain Res. 1996;73(1-2):109-16. doi: 10.1016/0166-4328(96)00079-4.
Medicinal chemists have traditionally looked to the biosynthetic diversity found in nature to provide structural templates for the development of novel therapeutic agents, and the field of hallucinogen chemistry is similar to other fields in this respect. Even LSD, for many psychopharmacologists the prototype hallucinogen, is not itself a natural compound but rather is a semisynthetic analogue of alkaloids found in plants and fungi. A similar statement could be made about the other major structural classes of hallucinogenic agents: the phenylethylamine derivatives, the tryptamine derivatives, and the beta-carboline derivatives. In each case, compounds occurring naturally in some plant, usually associated with a long tradition of ethnomedical or ceremonial use, have been the starting point for the synthesis of numerous analogues. Some of these, such as the methoxylated amphetamine derivatives, display a pharmacological profile that differs in important respects from their natural product templates. In some instances the analogues have proven to be useful tools in the hands of neurobiologists characterizing the structure and function of brain neurotransmitter systems; in other cases, they have led to the development of new psychopharmacological agents with realized or potential clinical utility. This paper gives a brief historical overview of the role of natural products in the history and development of medicinal chemistry and experimental pharmacology, particularly with respect to the development of psychopharmacology and the discovery of CNS-active agents. It discusses the potential for the discovery of new medications with psychotherapeutic and/or research applications though the investigation of plants and natural compounds with serotonergic activities. Finally, consideration is given to some lesser known plant hallucinogens which may provide further useful leads for psychotherapeutic drug discovery.
传统上，药物化学家一直从自然界中发现的生物合成多样性中寻找结构模板，以开发新型治疗药物，在这方面，致幻剂化学领域与其他领域类似。即使是麦角酸二乙酰胺（LSD），对许多精神药理学家来说它是致幻剂的原型，但它本身并非天然化合物，而是植物和真菌中发现的生物碱的半合成类似物。对于其他主要结构类别的致幻剂，即苯乙胺衍生物、色胺衍生物和β-咔啉衍生物，也可以做出类似的表述。在每种情况下，某些植物中天然存在的化合物，通常与悠久的民族医学或仪式用途传统相关联，一直是众多类似物合成的起点。其中一些，如甲氧基化苯丙胺衍生物，其药理学特征在重要方面与其天然产物模板不同。在某些情况下，这些类似物已被证明是神经生物学家手中用于表征脑神经递质系统结构和功能的有用工具；在其他情况下，它们促成了具有实际或潜在临床用途的新型精神药理药物的开发。本文简要概述了天然产物在药物化学和实验药理学的历史与发展中的作用，特别是在精神药理学的发展以及中枢神经系统活性药物的发现方面。它讨论了通过研究具有血清素能活性的植物和天然化合物来发现具有心理治疗和/或研究应用的新药物的潜力。最后，考虑了一些鲜为人知的植物致幻剂，它们可能为心理治疗药物的发现提供进一步有用的线索。
