Harmine, activity

The intense fluorescence of /3-carbolmium salts has been repeatedly noted (see, e.g., ref. 3). The wavelengths for maximum activation and emission of fluoreseenee have been determined for harmine, ... 

The N-alkylated harmine derivatives were prepared by simple alkylation of harmine anions (generated using sodium hydride) with alkyl halides and bromides. For example, 56 was prepared in 83% yield in this manner, and the N-methyl analog (which had similar antitumor activity to that of 56) was obtained in 80% yield using methyl iodide. 

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). 

The harmala alkaloids harmaline (368 X = NH) and harmi.ne (369 X = NH) are active reversible inhibitors of monoamine oxidase (MAO). Benzo[ Jthiophene analogs of harmaline (368 X = S) and harmine (369 X = S), when tested in vitro as inhibitors of rat liver MAO, showed that (368 X = S) was 50 times more potent than harmaline, but (369 X = NH or S) were equivalent in potency. The replacement of the indolic nitrogen by sulfur greatly increased the lipid solubility of the molecule, which was reflected in the physiological disposition of the two analogs. 

Active Constituents Harmine, haraline, harmalol, and tetrahydroharmine. Approximately 500 mg total alkaloids per 4 oz. cup prepared as above. 

Michael Valentine Smith suggests in Psychedelic Chemistry that harmaline and harmine are both active at about 200 mg. oral dosage. Jeremy Bigwood disputes this, saying that to get effective potentiation from the hydrochloride salts an adult should swallow at least 300 mg, harmaline or 500 mg. harmine. Shulgin puts the "effective dose range of harmaline at 70 to 100 mg. intravenously or 300 to 400 mg. orally. 

I d suggest that you try active doses of these alkaloids and attempt sex before writing this section. Or take it from me, harmine, harmaline, ayahuasca, DMT/harmaline, etc. are anaphrodisiacs. 

It is possible that the schizophrenic episode which followed our experiment may have resulted from an irreversible inhibition of MAO. Some MAO inhibitors used therapeutically as antidepressants (notably iproniazid) can bind irreversibly to the enzyme, triggering a long-term inhibition that can only be mitigated through the production of new enzymes by protein synthesis. Studies of irreversible inhibition have shown that full recovery of normal MAO activity can require a period of ten to twenty days (Planz et al. 1972). While harmine and its analogs are known to exhibit strong MAO inhibition, this action is reversible and is on the order of... 

The oral activity of tryptamines that are degraded by MAO can be enhanced by chemicals called monoamine oxidase inhibitors (MAOI). This synergism serves as the basis for the Amazonian entheogenic brew, ayahuasca (which means vine of the souls ), where DMT is rendered orally active by the presence of MAOI harmala alkaloids from the plant Banisteriopsis caapi (Metzner 1999). Anoliher botanical source of the MAOI harmala alkaloids harmaline and harmine is the seed of the Syrian rue, Beganum harmala, a bush related to the creosote, native to Asia and Africa. There are anecdotal reports that the potency of psilocybin... 

Harmine was evaluated for its effects on both arachidonic acid metabolism and human platelet aggregation (platelet-activating factor) and found to be inactive [269]. 

The effects of harmine, harmaline, and other harmala alkaloids on the contractions induced in the vascular smooth muscle of rabbit aorta and intestinal smooth muscle of taenia isolated from guinea-pig caecum were examined. The order of inhibitory potency was 6-methoxyharman = harmine > harmaline = 2-methylharmine = harmane > 6-methoxyharmalan > harmalol = harmol for contractions induced by high K+1 in aorta and taenia and by carbachol in taenia. The order of inhibitory potency for contractions induced by noradrenaline in the aorta were 2-methylharmine > 6-methoxyharman > 6-methoxyharmalan - harmol = harmalol = harmane > harmine > harmaline. The results suggest that harmaline inhibits the contractile response of rabbit aorta and guinea-pig taenia via inhibition of different types of Ca+2 channel. The structure-activity relationship indicates that the potency and selectivity of the inhibitory effects on these channels are varied by modification of the structure within this alkaloid series [270]. 

The structure inhibitory activity relationships among numerous P-carboline alkaloids was studied. Harmine was found to inhibit the actions of cyclic adenosine monophosphate (cAMP) phosphodiesterase (ICS0 69.3 x 10 5 M). Among the di- and tri-substituted P-carbolines, the O-methylated P-carbolines and the O-acetylated p-carbolines had higher inhibitory activity than the corresponding hydroxy p-carbolines, while the dihydro- and tetrahydro-derivatives were not potent inhibitors [271]. 

The potential cytotoxic activities of forty-six Strychnos alkaloids, including harmine, were tested on different cancer or normal cells cultured in vitro. At a concentration of 1-10 pg/ml, harmine showed modest activity against L 1210 cells derived from DB A/2 mouse ascites tumor and cultured HeLa cells derived from human carcinoma. The alkaloid displayed only slight activity against cultured flow 2002 cells derived from normal embryonic human lungs, and was inactive against cultured B16 melanoma cells derived from C57BL mouse melanoma [273]. 

It is significant to note that neither one of these plant substances by itself is normally psychoactive in oral doses. (Harmine/harmaline is said to effect hallucinosis at highly toxic levels, but in less heroic quantities it is at best a tranquilizer, at worst an emetic.) DMT, in any quantity, is not orally active unless used in combination with a monoamine oxidase (AAAO) inhibitor. This principle is precisely what makes ayahuasca effective the harmala alkaloids in the Banisteriopsis caapi vine are potent short-term MAO inhibitors which synergize with the DMT-containing Psychotria viridis leaves to produce what has been described as one of the most profound of all psychedelic experiences. 

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