Tryptamine-related hallucinogens

Tryptamine-related hallucinogens are naturally occurring plant alkaloids or their chemically synthesized derivatives. Some of them are related to sub-... 

Tryptamine itself is found in all major centers of the brain. Its physiologic role in central nervous system (CNS) function, however, remains unclear. 5-Hydroxytryptamine (5-HT, serotonin) is an important neurotransmitter in the CNS. The structural similarity of the tryptamine-related hallucinogens with 5-HT presumably forms the neurochemical basis for their action within the CNS. 

One of the best studied tryptamine derivatives is DMT (37). DMT and 5-OMeDMT (59) are probably the active constituents of a variety of South American hallucinogenic snuffs. These and related indolealkylamines have been detected in members of at least five different plant families Agaricaceae, Leg-uminosae, Malpighiaceae, Myristicaceae and Rubiaceae (107,109,110,187). In... 

Since they are tryptamine derivatives, the indolic hallucinogens are structurally related to the neurohumoral factor serotonin (5-hydroxytryptamine). Serotonin is widely distributed in warmblooded animals. It accumulates in the brain, where it plays a role in the biochemistry of nervous regulations. Consequently, it seems that certain tryptamine structures which occur so frequently in hallucinogens, as well as in the neurohormone serotonin, may be biochemically important in the metabolism of psychic functions. . . ... 

In what follows, mainly our own work is offered to support these assertions, although other persuasive examples exist. In the following sections we describe and exemplify our theoretical approaches to the study of drug activity, and their relation to the experimental results from our studies on the action of hallucinogens, mainly LSD and tryptamine derivatives. 

A grass found in East Africa. At certain seasons this plant contains bufotenine and related tryptamine alkaloids with hallucinogenic effects. Sheep eat the grass motor disturbances bufotenine acting on spinal pathways. Bufotenine blocks uptake of norepinephrine. Ventricular fibrillation can occur if animals become excited. 

The 5-O-methyl analc e of bufotenine (5-MeO-DMT) is parenterally active as a hallucinogen in humans, but is not orally active. 5-MeO-DMT exhibits similar psychological and somatic symptoms in humans as DMT, but is approximately an order of magnimde more potent on a milligram basis (see Table III). Both 5-MeO-DMT and bufotenine are closely related stmcturally to the CNS transmitter serotonin (5-hydroxytryptamine). The N,N-diisopropyl analogues of DMT and 5-McO-DMT are both orally active as hallucinogens in humans (Shu%in Carter 1980). Little is known of the hallucinogenic activity of the N-monosubstituted, N-dealkyl or N-cyclo-alkyl tryptamines. The mono-tert-butyl derivative is reputed to be orally active (Shubin 1982). 

Psilocybin 4-phosphoryloxy-V,V-dimethyl-trypt-amine, m.p. 220- 8°C. P. and the related compound psilocin (4-hydroxy-N,Ai-dimethyl-tryptamine, m.p. 173-176°C), are jointly responsible for the psychotropic action of the fruiting body of the Mexican hallucinogenic fungus Teonanacatl (Psihcybe mexiama). P. was the first naturally occurring phosphorylated indole derivative to be isolated. It can be hydrolysed to psilocin. Both compounds are slightly poisonous. Administered by mouth or by intramuscular injection, they cause hallucinations similar to those caused by LSD the latter is, however, about 100 times more potent. 

The many hallucinogenic indole alkaloids, for instance, are related to serotonin and 5-methoxy-tryptamine,... 

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