Indolealkylamines

FIGURE 13-1 Chemical structure of 5-hydroxytryptamine (5-HT serotonin) and related indolealkylamines. The indole ring structure consists of the benzene ring and the attached five-member ring containing nitrogen. 

In this chapter, we have reviewed the effects of indolealkylamine and phen-ylalkylamine hallucinogens on respondent (classical or Pavlovian) and operant (instrumental) behavior. Both the classically conditioned NMR and bar pressing or licking that is simultaneously reinforced with food or water and suppressed by punishment appear to be particularly sensitive to low doses of LSD- or mescaline-like agents. To date, however, neither of these behaviors has provided substantial amounts of information regarding specific, underlying neuronal mechanisms. 

Sloviter, R. S., Drust, E. G., Dammiano, B. P., and Conner, J. D. (1981) A common mechanism for lysergic acid, indolealkylamine and phenethylamine hallucinogens Serotonergic mediation of behavioral effects in rats. J. Pharmacol. Exp. Ther., 214 231-238. 

The conformational and quantum chemical properties of indolealkylamines have been investigated (see, e.g., refs. 9,35,61,94-96,112,126-130, and 177), but, to date, such studies have had a limited impact on the understanding of structure-activity relationships. Evidence suggests that the indolealkylamine side... 

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... 

Glennon, R. A., Young, R., and Jacyno, J. M. (1983) Indolealkylamine and phenalkylamine hallucinogens Effect of a-methyl and N-methyl substituents on behavioral activity. Biochem. Pharmacol., 32 1267-1273. 

Pullman, B., Courriere, P., and Berthod, H. (1974) Molecular orbital studies on the conformation of hallucinogenic indolealkylamines and related compounds. The isolated molecules and the solvent effect. J. Med. Chem.. 17 439-447. 

Vasko, M. R., Lutz, M. P., and Domino, E. F. (1974) Structure activity relations of some indolealkylamines in comparison to phenethylamines on motor activity and acquisition of avoidance behavior. Psychopharmacologia, 36 49-58. 

Ibogaine, discovery of, 7 Imagery, hallucinogen-induced, 15-16 Indole hallucinogens, effects of on spinal reflexes, 38-39 on startle reflexes, 43-44 Indolealkylamines... 

Seven groups of these drugs can be separated based on their various chemical f structures (a) lysergic acid derivatives, of which lysergide (LSD) is the prototype (b) phenylethylamine derivatives, of which 3,4,5-trihydroxyphenylethylamine (mescaline) is the prototype (c) indolealkylamines, such as 4-phosphorodi-methyltryptamine (psilocybin) (d) other indolic derivatives, such as the harmine... 

The effects of hallucinogens on the 5-HT syndrome have been extensively studied to date, every hallucinogen examined has been reported to produce the syndrome. This list includes LSD and related indolealkylamine [DMT, 5-MeODMT, diethyltryptamine (DET)] hallucinogens (39,53,56,67,108,152,155, 159,162,166,176,180,185,198), as well as phenethylamine (DOM, mescaline) hallucinogens (135,159,198). 

Anden, N. E., Corrodi, H and Fuxe, K. (1971) Hallucinogenic drugs of the indolealkylamine type and central monoamine neurons. J. Pharmacol. Exp. Ther., 179 236-249. 

This chapter considers the effects of indolealkylamine (LSD-like) and phenyl-alkylamine (mescaline-like) hallucinogens on learned behavior. We concentrate on those approaches that have shed the most light on underlying neuronal mechanisms or that show promise of becoming useful (in vivo) animal models of hallucinogenic drug action. Thus we are selective rather than exhaustive, a luxury made possible in part because several more empirically oriented reviews have been published recently (14,16,34,35). 

The neurotransmitter serotonin (21) has been implicated as playing a role in the mechanism of action of the hallucinogenic indolealkylamines however, the importance of other neurotransmitters cannot be ruled out at this time. Studies targeted specifically toward the elucidation of the mechanism of action of indolealkylamines are considered in other chapters, and this review is limited to a discussion of structure-activity relationships. 

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. 

Falkenberg, G. (1972) The Molecular Structure of Some Psychoactive Indolealkylamines and Related Substances. Thesis, Karolinska Institute, Stockholm. 

Dennis J. McKenna, David B. Repke, Leland Lo, and Stephen J. Peroutka. "Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes." Neuropharmacology 29 (1990) 193-98. 

Coppen A Depressive states and indolealkylamines, in Advances in Pharmacology, Vol 6. Edited by Garattini S, Shore PA. New York, Academic Press, 1968, pp 283-291... 

There are two main chemical categories of hallucinogens the indolealkylamine derivatives, wh ich are related to theneurotrans-mitter serotonin, and the phenethylamine derivatives, which... 

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