Harmalin

Armalin · Hartline · HARMALINE · Harmidine · NSC 407285 · Harmaline>Harmaline-RM · HARMALINE,99% · DIHYDROHARMINE

Identifikatoren & physikalische Daten

CAS No.	304-21-2
Summenformel	C13H14N2O
Durchschnittliche Molmasse	214,26 g/mol
Monoisotopische Masse	214,11061307 g/mol
SMILES	COc1ccc2c3c([nH]c2c1)C(C)=NCC3
InChIKey	RERZNCLIYCABFS-UHFFFAOYSA-N
PubChem CID	3564
ChEMBL	CHEMBL340807
ChEBI	CHEBI:28172
EC No.	206-152-6
DTXSID	DTXSID8041038
Lokaler Name	Harmalin

Chemische & physikalische Eigenschaften

XLogP	2,1
Polarare Oberfläche (TPSA)	37,4
H-Brücken-Donoren	1
H-Brücken-Akzeptoren	2
Frei drehbare Bindungen	1
Schwere Atome	16
Formalladung	0
Komplexität	302
Arzneimittel	DEA NFLIS-Drug Category -> StimulantsPharmaceuticals -> Listed in ZINC15
Color/Form	Orthorhombic bipyramidal prisms, tablets from methanol, rhombic octahedra from ethanol
Löslichkeit	Slightly soluble in water, alcohol, etherquite soluble in hot alcohol, dilute acidsSoluble in chloroform, pyridine30.6 [ug/mL] (The mean of the results at pH 7.4)Slightly soluble in waterDMF: 1.4 mg/mlDMF:PBS(pH 7.2)(1:1): 0.5 mg/mlDMSO: 0.25 mg/mlEthanol: 0.5 mg/ml
Human Drugs	Pharmaceuticals
Schmelzpunkt	229-231 °C250 - 251 °C232-234 °C(lit.)
Physical Description	Solid
Dissociation Constants	pKa = 4.2
Collision Cross Section	146.2 Å² [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]148.98 Å² [M+Na]+ [CCS Type: TW
Other Experimental Properties	Slender needles, moderately soluble in water, alcohol /Hydrochloride dihydrate/
Siedepunkt	354.4°C (rough estimate)
Dichte	1.0850 (rough estimate)
Brechungsindex	1.6450 (estimate)
Lagerbedingungen	-10 to -25°C
Aggregatzustand	powder
pKa (Säurekonstante)	4.2(at 25℃)
Farbe	Light orange to Yellow to Green
Merck	14,4613
BRN	207310
InChI	1S/C13H14N2O/c1-8-13-11(5-6-14-8)10-4-3-9(16-2)7-12(10)15-13/h3-4,7,15H,5-6H2,1-2H3
InChIKey	RERZNCLIYCABFS-UHFFFAOYSA-N
SMILES	COc1ccc2c3CCN=C(C)c3[nH]c2c1
LogP (Verteilungskoeffizient)	2.251 (est)
CAS Datenbank	304-21-2(CAS DataBase Reference)
NIST chemische Informationen	Harmaline(304-21-2)
EPA chemische Informationen	3H-Pyrido[3,4-b]indole, 4,9-dihydro-7-methoxy-1-methyl- (304-21-2)

Sicherheit & Vorschriften

GHS-Einstufung	This chemical does not meet GHS hazard criteria for 33.3% (1 of 3) of reports.WarningH302 (33.3%): Harmful if swallowed [Warning Acute toxicity, oral]P260, P264, P270, P301+P317, P308+P316, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard Classes and Categories	Acute Tox. 4 (33.3%)
Entsorgungsverfahren	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.
Natural Pollution Sources	... from seeds of Peganum harmala L., Zygophyllaceae ... from Banisteria caapi Spruce, Malpighiaceae
Human Toxicity Excerpts	/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.
Non-Human Toxicity Excerpts	/LABORATORY ANIMALS: Neurotoxicity/ Both harmaline and physostigmine are known to produce whole-body tremors in rodents, yet there is little quantitative information on the differential frequency characteristics of these tremors or on other possible motor effects of these drugs. In addition, the degree to which tolerance develops to their tremorogenic effects is uncertain. OBJECTIVES: The purpose of this work was to use a new kind of instrument (the force-plate actometer) to describe quantitatively the frequency characteristics of tremor induced by the two drugs and simultaneously to measure locomotor activity effects. Another aim was to detect any tolerance effects on the tremor or locomotor measurements. Sprague-Dawley rats in four separate groups received harmaline (0, 4.0, 8.0, and 16.0 mg/kg) while another four groups received physostigmine (0, 0.10, 0.25, and 0.50 mg/kg). Dosing continued for 4 consecutive days. Each day, every rat's whole-body tremor and locomotor activity were recorded for 30 min. Fourier analysis of the force-plate recordings was used to quantify tremor and characterize its frequency components. Harmaline induced a dose-related tremor that peaked in the 10 Hz region of the spectrum, while the dose related-tremor of physostigmine was demonstrably of a broader-band frequency composition. While harmaline tremor exhibited pronounced tolerance, physostigmine tremor remained substantial across the 4 days of dosing. Both drugs suppressed locomotor activity, and there was no tolerance on this measure for either drug. In regard to tremor, harmaline and physostigmine induced quantitatively different kinds of tremor, and these differences probably reflect the drugs' different sites of action in the brain (harmaline: inferior olivephysostigmine: basal ganglia). For harmaline, tolerance to the tremorogenic effect was concurrent with a lack of tolerance to locomotor suppression, and this finding suggested the presence of a strong motor effect of harmaline that continued to be expressed despite the absence of tremor./LABORATORY ANIMALS: Neurotoxicity/ beta-Carboline alkaloids are found in several medicinal plants and display a variety of actions on the central nervous, muscular and cardiovascular systems. The aim of the present study was to evaluate the effects of systemic administration of beta-carboline alkaloids on object recognition in mice. Adult Swiss mice received an intra-peritoneal injection (ip) of alkaloids (1.0, 2.5 or 5.0 mg/kg) 30 min before training in an object recognition task. The fully aromatic beta-carbolines, harmine and harmol, induced an enhancement of short-term memory (STM) at all doses tested when compared to controls. Harmaline, a dihydro beta-carboline and inverse agonist of the MK-801 binding site on the N-methyl-d-aspartate (NMDA) receptor, also induced an enhancement of both short-term memory (STM) and long-term memory (LTM). These results demonstrate that systemic administration of beta-carboline alkaloids can improve object recognition memory in mice./LABORATORY ANIMALS: Neurotoxicity/ A behavioral preparation especially sensitive to low-dose drug effects on fine motor behavior in rats was used to assess the tremorogenic effects of harmaline, an indole alkaloid and beta-carboline derivative. Rats that were trained to press downward on a force transducer for water reinforcement were initially administered harmaline (0.5 and 1.0 mg/kg) in an acute dosing regime. Immediately following the day of initial acute exposure to 1 mg/kg, 3 consecutive days at this dose ensued, providing for a 4-day, repeated-dosing analysis. Harmaline did not significantly suppress task engagement during either acute or repeated dosing. Acute administration of harmaline dose-dependently increased power in the high-frequency (10-25 Hz) band of the power spectrum (tremor) without affecting overall forelimb force output. Upon continued administration, tremor remained significantly elevated above vehicle values. Harmaline also slowed the rats' licking frequency, an effect that did not diminish with repeated dosing. Harmaline increased the durations of individual responses during acute dosing and continued to exert this effect with repeated dosing. The effects reported in the present study may represent low-dose harmaline-induced alterations in the olivo-cerebellar system./LABORATORY ANIMALS: Neurotoxicity/ Harmaline's effects on reflex and classically conditioned eyelid responses and on tremor picked up by a coil attached to the back were measured in alert cats. Harmaline at a dose of 10 mg/kg produced skeletal muscle tremogenic effects that lasted 4h. Back movements presented a tremor-like displacement with a frequency peak at 10 Hz, but lid responses oscillated as in controls, at 20 Hz during both reflex and conditioned eyelid movements, with no increase in oscillation amplitude or frequency. The learning curves of harmaline-injected animals remained as in controls, but eyelid conditioned responses showed longer latencies, and smaller amplitude and peak velocity. Reflex and already-learned eyelid responses were not modified by harmaline. These results imply that neuronal control systems for skeletal-motor and facial responses are differentially affected by harmaline.For more Non-Human Toxicity Excerpts (Complete) data for HARMALINE (13 total), please visit the HSDB record page.
Antidote and Emergency Treatment	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.
Wassergefährdungsklasse (WGK)	3
UN-Transportnummer	1544
Zollcode	2939.80.0000
RTECS-Nr.	UU9800000
R-Sätze (R)	25-20/21/22
Gefahrensymbole	Xn
Sicherheitshinweise (S)	22-24/25-36
Gefahrenklasse	6.1(b)Acute Tox. 3 DermalAcute Tox. 3 InhalationAcute Tox. 3 OralFlam. Liq. 2STOT SE 1
Verpackungsgruppe	III
Lagerklasse	3 - Flammable liquids
Gefahrstoffdaten	304-21-2(Hazardous Substances Data)

Anwendungen & Verwendung

Verwenden

CNS stimulant, antiparkinsonian agent