Beta carbolines

Myers RD, Melchior CL Differential actions on voluntary alcohol intake of tetra-hydroisoquinolines or a beta-carboline infused chronically in the ventricle of the rat. Pharmacol Biochem Behav 7 381-392, 1977 Naranjo CA, Sellers EM Clinical assessment and pharmacotherapy of the alcohol withdrawal syndrome, in Recent Developments in Alcoholism, Vol 4. Edited hy Galanter M. New York, Plenum, 1986... 

Venault P, Chapouthier G, de Carvalho LP, et al Benzodiazepine impairs and beta-carboline enhances performance in learning and memory tasks. Natme 321 864-866, 1986... 

Han, QP and Dryhurst, G (1996) Influence of glutathione on the oxidation of l-methyl-6-hydroxy-l,2,3,4-tetrahydro-beta-carboline chemistry of potential relevance to the addictive and neurodegenerative consequences of ethanol use. J. Med. Chem. 39 1494-1508. 

Murai, T., Koshikawa, N., Kanayama, T., Takada, K., Tomiyama, K., and Kobayashi, M., Opposite effects of midazolam and beta-carboline-3-carboxylate ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo microdialysis, Eur. J. Pharmacol., 261, 65, 1994. 

Mclsaac, W., Estevez, V. Structure-action relationship of beta-carbolines as monoamine oxidase inhibitors. Biochem. Pharmacol. 15 1625, 1966. 

The oxepine-fused beta-carboline 73 was synthesized in good yield (71%) from the diene precursor 72 using ring-closing metathesis and Grubbs I catalyst <06TL6895>. 

Structures 23, 24. Harman (82) and norharman (83) have been isolated from cigarette smoke (175), and Janiger and deRios (122) have suggested that some of the tobacco-induced altered states reported by South American Indians might be related to the cumulative effects of these beta-carbolines. 

Schultes, R. E. (1982) The beta-carboline hallucinogens of South America. J. Psychoactive Drugs, 14 205-220. 

In summary, based on the results of relatively limited studies, the dihydro beta-carboline, harmaline (80), is more active than either its fully unsaturated derivative harmine (79) or its reduced derivative tetrahydroharmine (81). The positional isomer of harmine, 6-methoxyharmalan (85), is slightly more potent than harmaline. Reduction to the tetrahydro derivative 86 reduces potency. Although thorough dose-effect studies have not yet been performed, none of the beta-carboline derivatives has been found to be significantly more potent than DMT (37). 

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. 

Sulfur Analogs of Harman and Other beta-Carbolines JACS 72,4999(1950)... 

To synthesize 6-methoxy-3,4-dihydro-beta-carboline (10-meth-oxy-harmalan), add 5-methoxy-tryptamine to acetic anhydride and let stand twelve hours at 10°. Dilute with water, basify and extract with methylene Cl and dry, evaporate in vacuum to get melatonin (I). Reflux (1) in xylene in the presence of P205 to get the title compounds. Other References JMC 7,136(1964) JPS 57,1364 (1968), 59,1446(1970) JACS 70,219(1948) JCS 1602(1921), 1203(1951), 4589,4593(1956) Organic Synthesis 51, 136... 

Harmaline and analogs BSC 2058(1973). Beta-carbolines from sugars and tryptamines in 1 step BER 106,2943(1973). 

Chermat R, Brochet D, DeFeudis FV, Drieu K. (1997). Interactions of Ginkgo biloba extract (EGb 761), diazepam and ethyl beta-carboline-3-carboxylate on social behavior of the rat. Pharmacol Biochem Behav. 56(2) 333-9. 

Ergene E, Schoener EP. (1993). Effects of harmane (1-methyl-beta-carboline) on neurons in the nucleus accumbens of the rat. Pharmacol Biochem Behav. 44 4951-57. 

Fernandez de Arriba A, Lizcano JM, Balsa MD, Unzeta M. (1994). Inhibition of monoamine oxidase from bovine retina by beta-carbolines. J Pharm Pharmacol. 46(10) 809-13. 

Clover V, Liebowitz J, Armando I, Sandler M. (1982). beta-Carbolines as selective monoamine oxidase inhibitors in vivo implications. J Neurai Transm. 54(3-4) 209-18. 

Grella B, Dukat M, Young R, Teitler M, Herrick-Davis K, Gauthier CB, Glennon RA. (1998). Investigation of hallucinogenic and related beta-carbolines. Drug Aicohol Depend. 50(2) 99-107. 

Heisley S, Rabin RA, Winter JC. (1998b). The effects of beta-carbolines in rats trained with ibogaine as a discriminative stimulus. EurJ Pharmacol. 345(2) 139-43. 

Mehta AK, Ticku MK. (1989). Benzodiazepine and beta-carboline interactions with GABAA receptor-gated chloride channels in mammalian cultured spinal cord neurons. J Pharmacol Exp Then 249(2) 418-23. 

Rommelspacher H, Nanz C, Borbe HO, Fehske KJ, Muller WE, Wollert U. (1980). 1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding. Naunyn Schmiedebergs Arch Pharmacol. 314(1) 97-100. 

Tse SY, Mak IT, Dickens BF. (1991). Antioxidative properties of harmane and beta-carboline alkaloids. Biochem Pharmacol. 42(3) 459-64. 

Tweedie DJ, Burke MD. (1987). Metabolism of the beta-carbolines, harmine and harmol, by liver microsomes from phenobarbitone- or 3-methylcholanthrenetreated mice. Identification and quantitation of two novel harmine metabolites. Drug Metab Dispos. 15(1) 74-81. 

MAO-inhibiting effect of these beta-carbolines caused the residual psilocybin to emerge into consciousness as a deep hallucinogenic experience. 

Zayed, R. and Wink, M. 2005. Beta-carboline and quinoline alkaloids in root cultures and intact plants of Peganum harmala. Zeitschrift fur Naturforschung C-A Journal of Biosciences, 60(5-6) 451 58. 

Dorow R, Horowski R, Paschelke G, Amin M (1983) Severe anxiety induced by EG 7142, a beta-carboline ligand for benzodiazepine receptors. Lancet 2 98-99 Erankland PW, Josselyn SA, Bradwejn J, Vaccarino PJ, Yeomans JS (1997) Activation of amygdala cholecystokinin B receptors potentiates the acoustic startle response in the rat. J Neurosci 17 1838-1847... 

Stephens DN, Schneider HH, Kehr W, et al Abecamil, a metabohcally stable anxio-selective beta carboline acting at benzodiazepine receptors. J Pharmacol Exp Ther 253 334-343, 1990... 

Dorow R, Horowski R, Paschelke G, et al. Severe anxiety induced by FG-7142, a beta-carboline ligand for benzodiazepine receptors. Lancet 1983 2 98-99. 

---