Harmaline

214.26

214.26

206-152-6

CN58I4TOET

407285

DTXSID8041038

Orthorhombic bipyramidal prisms, tablets from methanol, rhombic octahedra from ethanol

2933990090

33.6

4.64 (est)

Solid

1.3±0.1 g/cm3

250 °C (decomp)

426.4±45.0 °C at 760 mmHg

211.7±28.7 °C

1.647

30.6 [ug/mL]

Subcutaneous-rat LD50: 120 mg/kg; subcutaneous-mouse LD50: 120 mg/kg

Combustible; Fire breaks down toxic nitrogen oxide fumes

Henry's Law constant = 2.46X10-9 atm-cu m/mol at 25 °C (est)

pKa = 4.2

146.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 2.03X10-10 cu cm/molec-sec at 25 °C (est)|Slender needles, moderately soluble in water, alcohol /Hydrochloride dihydrate/

III

6.1(b)

1544

3

25-20/21/22

22-24/25-36

UU9800000

Xn

Treasury is low temperature, ventilated, dry; stored separately from food raw materials

P260, P264, P270, P309+P311, P405, P501

H371

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

highly toxic

... from seeds of Peganum harmala L., Zygophyllaceae ... from Banisteria caapi Spruce, Malpighiaceae

/EXPL THER/ Oxidative modification of low-density lipoprotein (LDL) particles has been implicated in the process of atherogenesis. Antioxidants that prevent LDL from oxidation may reduce atherosclerosis. We have investigated the protective effect of Peganum harmala-extract (P-extract) and the two major alkaloids (harmine and harmaline) from the seeds of P. harmala against CuSO4-induced LDL oxidation. Through determination of the formation of malondialdehyde (MDA) and conjugated diene as well as the lag phase, the extract (P-extract) and compounds were found to possess an inhibitory effect. Moreover, harmaline and harmine reduced the rate of vitamin E disappearance and exhibited a significant free radical scavenging capacity (DPPH*). However, harmaline had a markedly higher antioxidant capacity than harmine in scavenging or preventive capacity against free radicals as well as inhibiting the aggregation of the LDL protein moiety (apolipoprotein B) induced by oxidation. The results suggested that P. harmala compounds could be a major source of compounds that inhibit LDL oxidative modification induced by copper.

A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. (See all compounds classified as Central Nervous System Stimulants.)|A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414) (See all compounds classified as Monoamine Oxidase Inhibitors.)

Harmaline, a known type A monoamine oxidase (MAO) inhibitor in adult brain of various species was found to elevate whole brain levels of dopamine and serotonin (5-HT) in rat fetuses of mothers injected 2-4 hr before Caesarean delivery. Similar stimulatory effects were observed for the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG), however, no significant effect was obtained for norepinephrine. The dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA) were decreased with the same treatment. These results imply that harmaline or one of its metabolites may cross the placental barrier to affect the fetal brain system not merely as a type A MAO inhibitor (i.e., relatively 5-HT-specific), but possibly also as a stimulatory agent for aldehyde reductase or catechol-O-methyltransferase (COMT) or alternately as an agent inhibiting the conjugation, efflux, or turnover of biogenic amine metabolites such as MHPG.

The psychotropic beta-carboline alkaloids, showing high affinity for 5-hydroxytryptamine, dopamine, benzodiazepine, and imidazoline receptors and the stimulation of locus coeruleus neurons, are formed endogenously from tryptophan-derived indolealkylamines through the Pictet-Spengler condensation with aldehydes in both plants and mammals. Cytochromes P450 1A1 (18.5), 1A2 (20), and 2D6 (100) catalyzed the O-demethylation of harmaline, and CYP1A1 (98.5), CYP1A2 (35), CYP2C9 (16), CYP2C19 (30), and CYP2D6 (115) catalyzed that of harmine (relative activities). The dehydrogenation/aromatization of harmaline to harmine was not carried out by aromatase (CYP19), CYP1A2, CYP2C9, CYP2D6, CYP3A4, pooled recombinant cytochromes P450, or human liver microsomes (HLMs). Kinetic parameters were calculated for the O-demethylations mediated by each isozyme and by pooled HLMs. K(cat) (min(-1)) and Ku (uM) values for harmaline were: CYP1A1, 10.8 and 11.8; CYP1A2, 12.3 and 13.3; CYP2C9, 5.3 and 175; CYP2C19, 10.3 and 160; and CYP2D6, 39.9 and 1.4. Values for harmine were: CYP1A1, 45.2 and 52.2; CYP1A2, 9.2 and 14.7; CYP2C9, 11.9 and 117; CYP2C19, 21.4 and 121; and CYP2D6, 29.7 and 7.4. Inhibition studies using monoclonal antibodies confirmed that CYP1A2 and CYP2D6 were the major isozymes contributing to both harmaline (20% and 50%, respectively) and harmine (20% and 30%) O-demethylations in pooled HLMs. The turnover numbers for CYP2D6 are among the highest ever reported for a CYP2D6 substrate. Finally, CYP2D6-transgenic mice were found to have increased harmaline and harmine O-demethylase activities as compared with wild-type mice. These findings suggest a role for polymorphic CYP2D6 in the pharmacology and toxicology of harmine and harmaline.|Harmaline has known human metabolites that include Harmalol.

Three psychological active principles from the seeds of Peganum harmala L., harmine, harmaline and harmalol, showed vasorelaxant activities in isolated rat thoracic aorta preparations precontracted by phenylephrine or KCl with rank order of relaxation potency of harmine > harmaline > harmalol. The vasorelaxant effects of harmine and harmaline (but not harmalol) were attenuated by endothelium removal or pretreatment with a nitric oxide (NO) synthase Nomega-nitro-L-arginine methyl ester. In cultured rat aortic endothelial cells, harmine and harmaline (but not harmalol) increased NO release, which was dependent on the presence of external Ca2+. In endothelium-denuded preparations, pretreatment of harmine, harmaline or harmalol (3-30 microM) inhibited phenylephrine-induced contractions in a non-competitive manner. Receptor binding assays indicated that all 3 compounds interacted with cardiac alpha1-adrenoceptors with comparable affinities (Ki value around 31 - 36 microM), but only harmine weakly interacted with the cardiac 1,4-dihydropyridine binding site of L-type Ca2+ channels (Ki value of 408 microM). Therefore, the present results suggested that the vasorelaxant effects of harmine and harmaline are attributed to their actions on the endothelial cells to release NO and on the vascular smooth muscles to inhibit the contractions induced by the activation of receptor-linked and voltage-dependent Ca2+ channels. The vasorelaxant effect of harmalol was not endothelium-dependent.

Treatment: For patients with a "bad trip" or panic reaction, provide gentile reassurance and relaxation techniques in a quiet environment. Treat agitation or severe anxiety states with diazepam or midazolam. Butyrophenones such as haloperidol are useful despite a small theoretic risk of lowering the seizure threshold. Treat seizures, hyperthermia, rhabdomyolysis, hypertension, and cardiac arrhythmias if they occur. /LSD and other hallucinogens/|Specific drugs and antidotes. There is no specific antidote. Sedating doses of diazepam may alleviate anxiety, and hypnotic doses can induce sleep for the duration of the "trip". /LSD and other hallucinogens/|Decontamination. Most of these drugs are taken orally in small doses, and decontamination procedures care relatively ineffective and likely to aggravate psychological distress. Consider the use of activated charcoal ... only after recent (within 30-60 minutes) large ingestions. /LSD and other hallucinogens/|Enhanced elimination. These procedures are not useful. Although urinary acidification may increase the urine concentration of some agents, it does not significantly enhance total-body elimination and may aggravate myoglobinuric renal failure. /LSD and other hallucinogens/|For more Antidote and Emergency Treatment (Complete) data for HARMALINE (7 total), please visit the HSDB record page.

/CASE REPORTS/ Peganum harmala, commonly called "Syrian rue," is native to countries around the Mediterranean sea and western United States. Known for its sedative effects when consumed by farm animals, its seeds have stimulant and hallucinogenic effects at low doses (3-4 g when eaten) in humans. Its active ingredients harmaline and harmine have monoamine oxidase inhibitor properties. A 41-year-old female prepared a hot drink by boiling approximately 100 g of P. harmala seeds in water (10-20 times the recommended dose for "calming one's nerves"). Upon presentation to the emergency department, she was unconscious and had hypertension, tachycardia, and tachypnea. Hepatic and renal function markers were grossly elevated. After intubation, she improved with supportive care over the course of five days. Her level of consciousness, renal and hepatic markers gradually returned to normal. Poisoning with high doses of Peganum harmala can be life-threatening, although patients usually recover with supportive therapy alone.

3H-Pyrido(3,4-b)indole, 4,9-dihydro-7-methoxy-1-methyl-

Central nervous system stimulant|Prohibited noxious weed ... /introduced in the US/. /Peganum harmala L./

Pharmaceuticals