Harmaline activity

A positional isomer of harmaline, 6-methoxyharmalan (85), was found to be slightly more active than harmaline in disrupting conditioned avoidance behavior in rats (146). Gryglewski and co-workers (98) found that replacement of the 1-methyl group of 6-methoxytetrahydroharman (86) by aryl substituents diminished excitatory behavior and resulted in a series of agents that produced a generalized depressant effect. 

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). 

Motor effects Harmaline produces a motor tremor (8-14 Hz) through activation of cells in the inferior olive, which is blocked by noncompetitive NMDA antagonists (Du et al. 1997 Stanford and Fowler 1998). Harmaline tremor is also reversed by benzodiazepine agonists (Robertson 1980). The tremor is initiated by synchronous rhythms in the olivocere-bellar system and red nucleus (Lorden et al. 1988 Gogolak et al. 1977 Batini et al. 1980). The tremor is associated with increased cGMP in the cerebellum, and tolerance with a relative normalization of cGMP (Lutes et al. 1988). Rapid tolerance develops to this effect with repeated doses. 

Batini C, Bernard JF, Buisseret-Delmas C, Horcholle-Bossavit G. (1980). [Harmaline tremor activity of the interposito-rubral system and of the bulboponto-reticular formation]. C R Seances Acad Sci D. 291(11) 905-7. 

Lorden JF, Stratton SE, Mays LE, Oltmans GA. (1988). Purkinje cell activity in rats following chronic treatment with harmaline. Neuroscience. 27(2) 465-72. 

The drink ayahuasca is also a DMT-containing decoction, but the presence of some harmaline-containing plant is required to make it active by mouth. This area is discussed under harmaline, although there is some information to be found in the 5-MeO-DMT commentary section. And, there are several species of Acacia found in both Africa and Australia that contain DMT, but there is no native medical use that suggests psychotropic action. Most of this is part and parcel of the chapter, "DMT is Everywhere." Let s not repeat it here. 

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. 

Hochstein and Paradies (1957) suggest that, in addition, the alkaloids harmaline and d-tetrahydroharmine, discovered in B. caapi, "may have substantial psychotomimetic activity in their own right."... 

DMT usually has no effect when taken orally because it is inactivated in the stomach by an enzyme called monoamine oxydase. Adding harmaline blocks the effects of this enzyme and allows the drug to enter the user s system. To become active orally, DMT must be combined with monoamine oxydase inhibitors (MAOIs), a highly potent and potentially dangerous medication. 

I want to mention that this alkaloid is of special interest because of its close resemblance to substances derived from the pineal gland of mammals. In particular, 10-methoxy-harmaline, which may be obtained in vitro from the incubation of serotonin in pineal tissue, resembles harmaline in its subjective effects and is of greater activity than the latter. This suggests that harmaline (differing from 10-methoxy-harmaline only in the position of the methoxy group) may derive its activity from the mimicry of a metabolite normally involved in the control of states of consciousness. 

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. 

The structure of harman (II R = H) has been discussed already in connection with that of harmaline. Many additional syntheses of it and of its tetrahydro derivative have been recorded (39-44). Owing to the extremely active 2-position in the indole nucleus, cyclizations which yield quinolines from /3-phenethylamines proceed with greater ease from tryptamines, often yielding the tetrahydro bases under so-called physiological conditions (43, 44). A novel synthesis of harman depends upon... 

Harmaline (= 3,4-Dihydro- Passiflora incarnata (passion Activates G protein (alA-R,... 

Cells carefully control the homeostasis of their ion concentrations by the action of ion channels (Na, K , Ca " channels) and throu Na, K -ATPase and Ca -ATPase. These channels and pumps are involved in signal transduction, active transport processes, and neuronal and neuromuscular signaling. Inhibition of transport processes (ion channels, carriers) is achieved by (Table IV) acronycine, ervatamine, harmaline, quinine, reserpine, colchicine, nitidine, salsolinol, sanguinarine, stepholidine, caffeine, sparteine, monocrotaline, steroidal alkaloids, aconitine, capsaicine, cassaine, maitoxin, ochratoxin, palytoxin, pumiliotoxin, saxitoxin, sole-nopsine, and tetrodotoxin. 

In order to explain the Na stimulation of ATP synthesis driven by a diffusion potential the presence of a Na /H antiporter was proposed [175]. In this artificial system the acidification of the cytoplasm, which occurs in response to electrogenic potassium efflux, could be prevented by the antiporter. Subsequently, Na /H antiporter activity has been demonstrated in both Methanobacterium thermoautotrophicum [176] and in Methanosarcina harden [108]. An important result of these studies was that the Na /H antiporter could be inhibited by amiloride and harmaline, which have been described as inhibitors of eucaryotic Na" /H" antiporters [177]. Using these inhibitors it has been shown that an active antiporter is essential for methanogenesis from H2/CO2 [176,178]. The antiporter also accepts Li instead of Na, since Li stimulates CH4 formation from H2/CO2 in the absence of Na [176]. In subsequent studies the use of amiloride and the more potent derivative ethyl-isopropylamiloride permitted the discrimination of primary and secondary Na potentials generated in partial reactions of the CO2 reduction pathway. 

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... 

---