Harmaline 872 harmine

Nikam TD, Ebrahimi MA, Patil VA. (2009) Embryogenic callns cnltnre of Tribulus terrestris L. a potential source of harmaline, harmine and diosgenin. Plant Biotechnol Rep 3 243-250. 

Yage, a psychedelic drink used by natives and urban dwellers in northwestern South America, is made from the outer bark of this vine. Psychedelic constituents are harmaline, harmine and d -1,2,3,4- tetrahydro harmine. 

Hochstein and Paradies determined in 1957 that results from ingestion of yagi (without other botanical additives) came mainly from interaction of three molecules—harmaline, harmine and -1,2,3,4-tetrahydroharmine. These findings have been accepted since then by investigators of this plant family. 

Protein biosynthesis is essential for all cells and thus provides another important target. Indeed, a number of alkaloids have been detected (although not too many have been studied in this context) which inhibit protein biosynthesis in vitro. Emetine from Cephaelis ipecacuanha (Rubiaceae) is the most potent plant constituent other alkaloids with the same ability include harringtonine, homoharringtonine, cryptopleurine, tubulosine, hemanthamine, lycorine, narciclasine, pretazettine, pseudolycorine, tylocrepine, and tylopherine [5] and furthermore, ajmaline, berberine, boldine, cinchonine, cinchonidine, harmalin, harmin, lobeline, norharman, papaverine, quinidine, quinine, salsoline, sanguinarine,... 

Ajmaline, berbamine, berberine, boldine, cinchonine, cinchonidine, ergometrine, harmalin, harmin, lobeline, norharman, papaverine, quinidine, quinine, sanguinarine, and solanine affect more than one of the basic... 

Whereas most alkaloids appear to be specifically directed towards animals, others show a broader activity spectrum. For example, alkaloids with marked antibacterial activities include ajmaline, berberine, boldine, cinchonidine, cinchonine, harmaline, harmine, lobeline, narcotine, norharman, quinidine, quinine, sanguinarine, strychnine and yohimbine (see reviews [5, 73, 96]. Only the benzophenanthridine alkaloid... 

Banisteriopsis caapi (Spr. ex Briesb.) Malpighiaceae Dicotyledons Ayahuasca, caapi, yage Aerial parts Tetrahydroharmine, harmaline, harmine [17]... 

Tribulus terrestris L. Zygophyllaceae Dicotyledons Puncture vine Leaves Harmaline, harmine, nraharman, harman. [22, 23]... 

Contains small and highly variable amounts (<0.01-0.09%) of indole alkaloids, consisting mainly of barman, with lesser amounts of har-mol, harmaline, harmine, and harmalol. Presence of the last four alkaloids has been disputed, but their presence was later confirmed at a total concentration of 0.7 ppm for all five alkaloids. ... 

On reduction harmaline yields tetrahydroharmine, C13HJ5ON2, m.p. 199°, and on gentle oxidation is converted into harmine. ... 

Constitution of Harmine and Harmaline. Harmaline is a dihydro-harmine. Both bases on reduction yield tetrahydroharmine and in both the single oxygen atom is present as methoxyl. Knowledge of the constitution of the two alkaloids is mainly due to the work of O. Fischer and his colleagues, and more recently to the researches of Perkin and Robinson. 

In view of its possible interest as the mode of formation of harman, harmine and harmaline in plants, Kermack, Perkin and Robinson investigated the conversion of tryptophan (II) into harman (I) and nor-harman (IV). The latter is produced when tryptophan is condensed with formaldehyde in presence of dilute sulphuric acid and the product (III) oxidised by potassium dichromate. Harman is formed when formaldehyde in this process is replaced by acetaldehyde. 

Since 1921 much work has been done to confirm the formula for harmine and that provisionally assigned to harmaline, both by synthetic methods and by reactions to explore and explain peculiarities in the... 

Spath and Lederer have published a simplified synthesis of harmaline consisting in treating the acetyl derivative of 6-methoxytryptamine (XXIX) with phosphorus pentoxide in boiling xylene, the harmaline thus produced being converted into harmine by catalytic dehydrogenation at 200°. 

In the course of structural investigations of a number of jS-carboline alkaloids, reactions leading to ring cleavage have been encountered. Oxidation of harmine (271) and of harmaline... 

These authors formulated the major steps in the biogenesis of the harmala bases as a condensation of a tryptamine derivative (460) with acetaldehyde to yield a l,2,3,4-tetrahydro-)3-carboline (461), which on oxidation in two stages would give harmaline (462 R = OCH3) and then harmine (463 R = OCH3). 

Fig. 31. Example of neuroactive indole alkaloids from plants. Note the similitude of chemical structure of harmine, harmaline, and serotonin.

The family Zygophyllaceae is made up of 30 genera and 250 species of shrubs known to have the tendency to elaborate a series of serotonin-like psychedelic indole alkaloids such as harmine, harmol, and harmaline, notably found in the seeds of a medicinal... 

P-Carboline alkaloids (harmaline, har-malol, harmane, harmol, harmine) 0.3-150 0.25-90 2.9-3.1 Harmaline was determined in plasma samples DNPO was used as aryl oxalate 45... 

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). 

Mancini 1988). Flavonoids vary across the ontogenic cycle, with the highest concentration of isovitexin occurring between preflowering and flowering stages. The indole alkaloids are small amounts (up to 0.01%), including harman, harmine, harmaline, and harmalol (Tyler 1994). Mechanisms of Action... 

Banisteriopsis caapi The primary hallucinogenic constituents of B. caapi are the jS-carbolines. These include harmaline, tetrahydroharmine, harmol, harmic acid methyl ester, harmic amide, acetyl norharmine, harmine A/-oxide, harmalinic acid, and ketotetrahydronorharmine (figure 9.8). B. rusbyana also contains DMT, as well as A/-methyltryptamine, 5-methoxy-N,/V-dimethyltryptamine, and 5-hydroxy-N,/V-dimethyltryptamine (bufotenin). /V-methyltetrahydro-jS-carboline is found in trace amounts. 

Harmala alkaloids are inhibitors of brain MAO. Harmane inhibits MAOA in the submicromolar range (5 X 10-7 M) and MAOB in the micromolar range (5 x 10-6 M) (Glover et al. 1982). Harmine inhibits MAOA, but also has additional unspecified monoamine modulatory effects (Meneguz et al. 1994 Fernandez de Arriba et al. 1994). Harmaline or its metabolites may also stimulate aldehyde reductase or catechol 0-methyltransferase (COMT) (Okonmah et al. 1988). 

GABAA benzodiazepine j8-carbolines act as inverse agonists of the GABAA benzodiazepine receptor (Mehta and Ticku 1989). Whereas benzodiazepines such as diazepam stimulate Cl- influx, j8-carbolines inhibit it. Harmine, harmaline, harmane, and harmalol inhibit flunitrazepam binding in the micromolar range (half-maximal inhibition between 28 and 130 pM) (Mousah et al. 1986). Endogenous j8-carbolines, such as harmane, have also been found in the human brain, but their endogenous functions are uncertain (Tse et al. 

Ingestion of yage in healthy volunteers yields plasma concentrations of 10 to 250 ng/mL for harmine and 1.0 to 25.0 ng/mL of harmaline (Callaway et al. 1996). The dose-concentration relationships are linear in this range. DMT shows linear dose-concentration relationships for plasma concentrations between 5 and 1000 ng/mL. Systemically administered j8-carbolines penetrate brain tissue, with relatively even distribution (Moncrieff 1989). DMT taken alone is not absorbed well orally. It may be taken as a snuff or smoked, or mixed with other plants to improve absorption. 

Autonomic effects Harmala alkaloids, as well as isolated harmine and harmaline, produce a dose-dependent hypothermia (Abdel-Fattah et al. 1995). This effect is serotonin-dependent, and partly mediated by 5-HTlA receptors. 

Cardiovascular effects Harmala alkaloids have cardiovascular effects (Aarons et al. 1977). Harmine, harmaline, and harmalol decrease heart rate, but increase pulse pressure, peak aortic flow, and myocardial contractile force in dogs. Harmine reduces systemic arterial blood pressure and peripheral vascular resistance. Vascular resistance effects are not mediated by jS-adrenergic or histamine HI receptors. 

Aarons DH, Rossi GV, Orzechowski RF. (1977). Cardiovascular actions of three harmala alkaloids harmine, harmaline, and harmalol. J Pharm Sci. 66(9) 1244-48. 

Moncrieff J. (1989). Determination of pharmacological levels of harmane, harmine, and harmaline in mammalian brain tissue, cerebrospinal fluid, and plasma by high-performance liquid chromatography with fluorimetric detection. J Chromatogr. 496(2) 269-78. 

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