Hallucinogens tryptamines

A 25-year-old white man was found dead the morning after he had consumed herbal extracts containing beta-carbolines and hallucinogenic tryptamines (14). No anatomical cause of death was found at post-mortem examination. N,N-dimethyltryptaminc (0.02 mg/1), 5-methoxy-N,N-dimethyltryptamine (1.88 mg/1), tetra-hydroharmine (0.38 mg/1), harmaline (0.07 mg/1), and harmine (0.17 mg/1) were found in post-mortem blood. 

Clare, B.W. (2004) A novel quantum theoretic QSAR for hallucinogenic tryptamines a major factor is the orientation of n orbital nodes. /. Mol. Struct. (Theochem), 712, 143-148. 

In 2009, the Brazilian Federal Police identified a new compound in seized blotters 9,10-dihydro-LSD, an uncontrolled drug [42], The structure of 9,10-dihydro-LSD (325 Da) differs from that of LSD (323 Da) in the hydrogenation of the 9,10 double bond (Figure 16.15). Clare [43] studied the activity of a series of hallucinogenic tryptamines as a function of various parameters such as lipophilidty, amine substituents, and orientation of nodes of occupied ir-like orbitals. The author reported that 9,10-dihydro-LSD is an inactive substance (activity = 0 MU), while LSD is a potent hallucinogen with an activity of 4000 MU. The results obtained for... 

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. 

Further evidence for serotonergic mediation of the effects of hallucinogens was provided by a report on the development of functional supersensitivity in the rat with a chronic denervation of spinal 5-HT neurons. Nygren et al. (138) reported that rats pretreated with intracistemally administered 5,6-dihydroxy-tryptamine (5,6-DHT), a 5-HT neurotoxin, subsequently showed greater hindlimb extensor facilitations to 5-MeODMT or L-tryptophan + nialamide at 1 week versus 1 day following pretreatment. 

Commissaris, R. L., Lyness, W. H., Moore, K. E., and Rech, R. H. (1981) Central 5-hydroxy-tryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats. Pharmacol Biochem. Behav., 14 595-601. 

TABLE 3. Structures of tryptamine derivatives which have been studied tor potential hallucinogenic activity... 

In summary, primary amine and monoalkyl derivatives of tryptamine have not yet been demonstrated to produce hallucinogenic effects in man or to consistently produce profound behavioral effects in animals. Admittedly, relatively few compounds have been examined, and few studies have been conducted. Nevertheless, present evidence suggests that these derivatives, by virtue of their inability to penetrate the blood-brain barrier and/or their rapid metabolism, may not be able to achieve adequate brain levels to elicit effects. In some cases, these factors may lead to masking of potential central effects by peripheral actions of the compounds or their metabolites. 

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... 

Taken together, the data presented here show that many phenyl- and in-dolealkylamines are hallucinogenic in man and behaviorally active in animals. In both series, primary amines penetrate the blood-brain barrier with difficulty, although this seems to be more of a problem with tryptamines (and even N-monoalkyltryptamines) than with phenethylamines. This situation is somewhat alleviated in the presence of an alpha-methyl substituent. The primary amines are also prone to rapid metabolism by oxidative deamination. Metabolism, however, can be impeded by the presence of an alpha-methyl or N-alkyl function. 

For the purposes of this chapter, hallucinogens are divided into two separate categories. The first section covers the substituted phenylalkylamines, with the prototype for these structures being mescaline. The second category includes indole-based compounds, including various substituted tryptamines, beta-car-bolines, and LSD. 

The 5-hydroxy derivative of DMT, bufotenine, or N,N-dimethyl-serotonin, is another naturally occurring tryptamine found to occur in South American snuffs. Intravenous administration of bufotenine (53) was reported by Fabing and co-workers (59,60) to be hallucinogenic in man. This finding is in conflict with a later report by Turner and Merlis (235). Apparently, due to its low lipid... 

Compounds such as LSD or the beta-carbolines do not possess a primary amino group, are not rapidly metabolized in comparison to, for example, tryptamine, and enter the brain readily certain substituent groups can alter this situation. Members of the phenylalkylamine and indolealkylamine families of hallucinogens can produce similar effects in animals but may be capable of producing distinctive effects in man. As yet, there is no satisfactory and comprehensive structure-activity relationship that encompasses both major classes of compounds. This may be due in part to unique metabolic and distributional characteristics associated with the individual ring systems. 

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