Harmine

Harmine is a natural dual-specificity tyrosine phosphorylation-regulated kinase ((DYRK)) inhibitor with anticancer and anti-inflammatory activities.

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> DYRK

Signaling Pathways >> Cell Cycle/DNA Damage >> RAD51

Research Areas >> Cancer

Natural Products >> Alkaloid

Research Areas >> Neurological Disease

5-HT2A Receptor:397 nM (Ki)

DYRK1A

RAD51

Harmine is an inhibitor of 5-HT2A, with an Ki of 397 nM[1]. Harmine inhibits tau phosphorylation by DYRK1A by selected DANDYs, with an IC50 of 190 nM[2].Harmine negatively regulates HR by interfering Rad51 recruitment, resulting in severe cytotoxicity in hepatoma cells. Furthermore, NHEJ inhibitor Nu7441 markedly sensitizes Hep3B cells to the anti-proliferative effects of Harmine[3].

It is shown that brain water content is significantly increased in the TBI group. Treatment with Harmine significantly reduces the tissue water content at 1, 3 and 5 days, compared with the TBI group. Harmine treatment significantly reduces the escape latency at 3 and 5 days, compared with the TBI group. Post-TBI administration of Harmine significantly improves the motor function recovery of the rats at 1, 3 and 5 days following TBI, compared with the TBI group without Harmine treatment. The neuronal survival rate in the Harmine-treated group is significantly increased, compared with the TBI group. Administration of Harmine results in marked elevation in the expression of GLT-1, compared with the TBI group. The administration of Harmine significantly reduces the expression of caspase 3, compared with the TBI group[4].

Rats[4] A total of 150 male Sprague-Dawley rats (age, 10-12 weeks; weighing, 280-320 g; are used in the present study. The rats are randomly divided into three groups: Sham-operated group (sham; n=15); the TBI group (TBI; n=35) and the TBI + Harmine-treated group (Harmine; n=35). Harmine is administered immediately following TBI (i.p, 30 mg/kg per day) for up to 5 days. The sham and TBI groups receive equal volumes of 0.9% saline solution (i.p.). The rats are grouped as follows for examination of behavioral recovery: Sham, n=3; TBI, n=7; and Harmine, n=7. Following TBI, the NSS is evaluated at 1, 3 and 5 days. Each rat is assessed by an observer who is blinded to the animal treatment[4].

[1]. Glennon RA, et al. Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors. Drug Alcohol Depend. 2000 Aug 1;60(2):121-32.

[2]. Neumann F, et al. DYRK1A inhibition and cognitive rescue in a Down syndrome mouse model are induced by new fluoro-DANDY derivatives. Sci Rep. 2018 Feb 12;8(1):2859.

[3]. Zhang L, et al. Harmine suppresses homologous recombination repair and inhibits proliferation of hepatoma cells. Cancer Biol Ther. 2015;16(11):1585-92.

[4]. Zhong Z, et al. Treatment with harmine ameliorates functional impairment and neuronal death following traumatic brain injury. Mol Med Rep. 2015 Dec;12(6):7985-91.

T0070907 | Pimavanserin | Serotonin hydrochloride | RS-1 | Sodium Ferulate | RI-1 | Thioridazine hydrochloride | Brexpiprazole | Risperidone | TG6-10-1 | AZ 191 | Cariprazine | Quetiapine | SERTINDOLE | TC-S 7004

DATA ITEMS CITED :

11

MOLECULAR FORMULA :

C13-H12-N2-O

MOLECULAR WEIGHT :

212.27

WISWESSER LINE NOTATION :

T B656 EN HMJ F1 KO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

3 mg/kg

TOXIC EFFECTS :

Behavioral - sleep Behavioral - tremor Gastrointestinal - nausea or vomiting

REFERENCE :

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 129,133,1928

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PSCBAY Psychopharmacology Service Center, Bulletin. (Bethesda, MD) V.1-3, 1961-65. For publisher information, see PSYBB9. Volume(issue)/page/year: 2,17,1963

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

243 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Skin and Appendages - hair

REFERENCE :

PCJOAU Pharmaceutical Chemistry Journal (English Translation). Translation of KHFZAN. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) No.1- 1967- Volume(issue)/page/year: 10,1171,1976

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 129,133,1928

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

10 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 129,133,1928

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 129,133,1928

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

60 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - excitement Behavioral - ataxia

REFERENCE :

NEPHBW Neuropharmacology. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.9- 1970- Volume(issue)/page/year: 10,15,1971

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 129,133,1928

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Amphibian - frog

DOSE/DURATION :

300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

QJPPAL Quarterly Journal of Pharmacy & Pharmacology. (London, UK) V.2-21, 1929-48. For publisher information, see JPPMAB. Volume(issue)/page/year: 9,37,1936 *** REVIEWS *** TOXICOLOGY REVIEW PISDDJ Pacific Information Service on Street Drugs. (J.K. Brown, School of Pharmacy, Univ. of the Pacific, Stockton, CA 95211) V.1- 1972(?)- Volume(issue)/page/year: 5(3-6),-,1977 TOXICOLOGY REVIEW CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 12,1,1978