Carboline

Carboline is a class of nitrogen-containing heterocyclic compounds in which a pyridine ring is fused to an indole or indole-like nucleus, yielding the core structure of beta-carbolines. The parent system is often described as 9H-pyrido[3,4-b]indole, and the term carboline sometimes refers broadly to related fused-ring compounds. The most studied subset is the beta-carbolines, which occur both as natural alkaloids and as synthetic derivatives.

Natural occurrence and examples are best known for beta-carbolines such as harmine, harmaline, and norharmane. These compounds are found in several plant sources, notably Banisteriopsis caapi and Peganum harmala, and can appear in trace amounts in other species. They are also encountered in certain foods and beverages where they may arise as minor constituents or during processing.

Pharmacology and applications: beta-Carbolines are notable for their activity as monoamine oxidase A inhibitors, with some acting reversibly. This MAOI activity contributes to pharmacological effects observed when beta-carboline–containing plants are consumed with other psychoactive substances, such as in ayahuasca preparations that combine with DMT. Beyond psychoactivity, beta-carbolines have been explored in medicinal chemistry for potential antidepressant, anticancer, and CNS-active roles, though none are approved as mainstream medicines.

Chemistry and synthesis: In the laboratory, beta-carbolines are commonly prepared by Pictet-Spengler cyclization of tryptamine or related indoleamines with aldehydes or ketones to give tetrahydro-β-carbolines, followed by oxidation to the aromatic β-carboline core. Numerous substituted derivatives exist, enabling structure–activity studies.

Safety and regulation: Because of MAOI activity, beta-carbolines can interact with serotonergic drugs and tyramine-containing foods, posing risks such as hypertensive events or serotonin syndrome in some contexts. Handling and use are subject to chemical safety protocols and, in some jurisdictions, regulatory controls.