Bufotenin

Bufotenine hydrogen oxalate [2963-79-3] M 294.3, m 96.5 . Crystd from Et20. 

Serotonin, A-methylserotonin, bufotenine, and 5-methoxy-A-methyltryptamine become readily available in a simple way by applying nucleophilic substitution reactions in 1-hydroxytryptamine chemistry (99H1157, 2001CPB87). 

Bromothymol blue reagent 45 Brucine 60, 67, 315, 316 Bufotenine 380 Bunitrolol 429... 

OH-DMT (Bufotenine) can cause severe physical discomfort including circulatory distress, nausea, psychological distress (panic and fear), severe skin flushing, and has the possibility of being fatal. 

Using tactile startle, bufotenin, a hallucinogen that does not cross the blood-brain barrier readily, also produced biphasic dose-response effects when given intraventricularly (76). After systemic administration, however, low doses of indole hallucinogens have not been reported to increase tactile startle (73). Thus LSD (20-80 Mg/kg), DMT (0.25-1.0 mg/kg), and psilocin (2.5-5.0 mg/kg) did not increase tactile startle. A slightly higher dose of LSD (100 Mg/kg) did increase startle toward the end of the test session, perhaps because of blocking habituation (see below). 

Opposite effects of intraventricular serotonin and bufotenin on rat startle responses. Pharmacol. Biochem. Behav., 3 687-691. 

Bufotenine has been found to be behaviorally inactive, or only weakly active, in most animal studies, although at 15 mg/kg, it did produce the head-twitch resonse in mice (43). It was also behaviorally active in experiments in which the blood-brain barrier was bypassed (78). Acylation of the polar hydroxy group of bufotenine increases its lipid solubility (65,74) and apparently enhances its ability to cross the blood-brain barrier (64). For example, O-acetylbufotenine (5-acetoxy-N,N-dimethyltryptamine 54) disrupted conditioned avoidance behavior in rodents (65) and produced tremorigenic activity similar to that elicited by DMT (37) or 5-OMeDMT (59) when administered to mice (64). In this latter study, a comparison of brain levels of bufotenine after administration of O-acetylbufotenine with those of DMT and 5-OMeDMT revealed bufotenine to be the most active of the three agents, based on brain concentration. The pivaloyl ester of bufotenine also appears to possess behavioral activity, since stimulus generalization was observed when this agent was administered to animals trained to discriminate 5-OMeDMT from saline (74). 

There are only two reports of the human evaluation of a 6-hydroxylated N,N-dialkyltryptamine. Szara and Hearst (223) studied the effects of 6-hydroxy-N,N-diethyltryptamine (6-OH-DET 56) in a single subject. Doses of 1 and 2 mg were inactive a 5-mg dose produced a short-lasting perceptual disturbance and a 10-mg dose, after 1 hr, produced some psychotomimetic disturbances. Rosenberg et al. (182) compared the activity of DMT with that of 6-OH-DMT (55) in five human subjects. While DMT was active, the 6-hydroxy derivative was found to be inactive at intramuscular doses of approximately 50 to 75 mg. At a dose of 10 mg/kg, 6-OH-DMT (55) increased spontaneous activity in mice more so than a comparable dose of DMT 6-OH-DET (36) was essentially equiactive with DET in this respect (224). In most other animal studies, however, 6-hydroxylation of DMT has been observed to result in a decrease or complete loss of behavioral activity (228,236-238). The behavioral potency of 5-OMeDMT (59) was also reduced by 6-hydroxylation (226). 7-Hydroxy-N,N-dimethyltrypt-amine (7-OH-DMT 57) has not been evaluated in man. At an intraperitoneal dose of 33 jtM/kg, 7-OH-DMT displayed no behavioral effects in rats (228). The pharmacologic effects of all four hydroxylated derivatives of DMT, psilocin (49), bufotenine (53), 6-OH-DMT (55), and 7-OH-DMT (57) have been compared in studies by Taborsky et al. (228) and by Cerletti et al. (29). 

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... 

Gessner, P. K., and Dankova, J. (1975) Brain bufotenine from administered acetylbufotenine Comparison of its tremorigenic activity with that of N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine. Pharmacologist, 17 259. 

In general, in animal research, it is well to be cautious, whether bufotenin or 5-methoxylated tryptamines or other substances postulated to be useful hallucinogenic tools are used and to be aware of the status of knowledge of their effects in humans, let alone on a characteristic battery of effects in animals. In rat, for example, 5-methoxytryptamine (20 mg/kg) appeared to markedly increase 5-HT metabolism as judged by 5-HIAA, although interfering factors in measurement were not ruled out (29). 

More than twenty indole derivatives have been identified from bufonid skin extracts. The indolylalkylamines bufotenidine, bufotenine, de-hydrobufotenine, bufo-tionine and serotonin (5-hydroxytryptamine) (Fig. 39.2b) have been identified in skin secretions of Bufo marinus, while the latter four have been detected in parotoid gland secretions (Erspamer 1994 Maciel, Schwartz, Pires Jr, Sebben, Castro, Sousa, Fontes and Schwartz 2003). The concentration of serotonin in the dried secretion of B. marinus was found to equate to approximately 0.1% of the total composition and primarily acts as a vasoconstrictor (Gregerman 1952 Toledo and Jared 1995). 

If the alkyl side chain at the 3 position of the indole nucleus is shortened (e.g., gramine) or lengthened (e.g., 3-(3-dimethylamino)-propyl indole) activity seems to decrease strikingly. Also, as the substituents are moved around the benzene ring of indole, activity decreases greatly in the order 4,5,6,7. For example, whereas 4-OH-DMT(psilocin) is active at about 5 mg orally (i.e., about as active as STP), 5-OH-DMT(bufotenin) is not psychedelic at all. 

This method, although described for indoles, probably also worlds with 5-OH-tryptamine (serotonin), and 5-OH-DMT (bufotenin) with compounds of the latter type, orally active psilocybin analogs will be obtained in one step. Dissolve 5 g 5-OH-indole (or analog) in 25 ml ethanol. Add 5.5 g 33% aqueous dimethylamine (or other amine, e.g., piperidine) and add slowly dropwise with stirring 3.5 g 38% aqueous formaldehyde. Two minutes after the end of the addition shake with water and CHCI3 dry and evaporate in vacuum the CHClj phase to get 5 g oily 4-dimethyl-aminomethyl-5-OH-indole (1) (can chromatograph on 100 g alumina and elute with ethyl acetate). It has been claimed that this method does not work. 

Synthese des 5,6,7-Trimethoxy-indols und des 6,7-Dimethoxy-bufotenin methyl-athers, by E. Hardegger and H. Corrodi, Pharm. Acta Helv., 39 (1964) 101-107. 

---