Maprotiline

Maprotiline is a highly selective noradrenergic reuptake blocker, has strong antidepressant efficacy. Maprotiline induces cancer cells apoptosis by targeting ERK signaling pathway and CRABP1. Maprotiline restrains cell proliferation and metastasis, exhibits anticancer effect[1][2].

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Neurological Disease

Maprotiline (10 μM) enhances the sensitivity of HCC cells to sorafenib (2 μM) and induces apoptosis[2]. Maprotiline (0, 10, or 20 μM for 72 h) works on ERK pathway and inhibits phosphorylation of SREBP2 in HepG2 and Huh7 cells[2]. Maprotiline may targets CRABP1 and regulate cholesterol biosynthesis in HCC cells[2]. Cell Invasion Assay[2] Cell Line: The human HCC cell lines Huh7 and HepG2 Concentration: 0, 10, 20 μM Incubation Time: 24 hours Result: Restrained HCC cells migration with inhibition of epithelial-mesenchymal transition (EMT). Cell Viability Assay[2] Cell Line: The human HCC cell lines Huh7 and HepG2 Concentration: 0, 10, 20 μM Incubation Time: 0, 24, 48, 72, 96, 120 hours Result: Triggered cell apoptosis and inhibited the cell viability of Huh7 and HepG2 cells in a dose- and time-dependent manner. Western Blot Analysis[2] Cell Line: The human HCC cell lines Huh7 and HepG2 Concentration: 0, 10, 20 μM Incubation Time: 72 hours Result: Inhibited cholesterol biosynthesis in HCC Cells.

Maprotiline (intraperitoneal injection; 3, 10, or 30 mg/kg) combinds with the synthetic cannabinoid WIN 55,212-2 and effectively reduces neuropathic pain[1]. Maprotiline (intraperitoneal injection; 0, 20, or 40 mg/kg; twice a week; 3 weeks) shows low toxicity and side effects on the organs, immune system and hematopoietic function[2]. Maprotiline (intraperitoneal injection; 0, 20, or 40 mg/kg; twice a week; 3 weeks) restrains cholesterol biosynthesis to inhibit growth and metastasis of HCC cells by interacting with CRABP1[2]. Animal Model: Male Balb-c mice (25–30 g)[1] Dosage: 3, 10, 30 mg/kg Administration: Intraperitoneal injection; evaluation 30 minutes after treatment Result: Attenuated pain-related behaviours in neuropathic mice. Animal Model: Nude mice (BALB/C nu/nu, 4–6 weeks old, female)[2] Dosage: 40 mg/kg Administration: Intraperitoneal injection; twice a week; 3 weeks Result: Decreased the cholesterol levels in serum and tumors and suppressed the growth of Huh7-derived tumor xenografts without obvious toxic effect.

[1]. Gunduz O, et al. Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice. Eur J Pain. 2016 Mar. 20(3):465-71.

[2]. Zheng C, et al. Maprotiline Suppresses Cholesterol Biosynthesis and Hepatocellular Carcinoma Progression Through Direct Targeting of CRABP1. Front Pharmacol. 2021 May 20. 12:689767.

MOLECULAR FORMULA :

C20-H23-N

MOLECULAR WEIGHT :

277.44

WISWESSER LINE NOTATION :

L6 H666/GP 2AF P&&TTJ O3M1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

26 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - coma Vascular - BP elevation not characterized in autonomic section

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 2,260,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

760 mg/kg

TOXIC EFFECTS :

Behavioral - muscle weakness Behavioral - ataxia Behavioral - muscle contraction or spasticity

REFERENCE :

HEPHD2 Handbook of Experimental Pharmacology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.50- 1978- Volume(issue)/page/year: 55,527,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

105 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - muscle weakness Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

APPHAX Acta Poloniae Pharmaceutica. For English translation, see APPFAR. (Ars Polona, POB 1001, 00-680 Warsaw 1, Poland) V.1- 1937- Volume(issue)/page/year: 40,235,1983

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

38 mg/kg

TOXIC EFFECTS :

Behavioral - muscle weakness Behavioral - ataxia Behavioral - muscle contraction or spasticity

REFERENCE :

HEPHD2 Handbook of Experimental Pharmacology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.50- 1978- Volume(issue)/page/year: 55,527,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

660 mg/kg

TOXIC EFFECTS :

Behavioral - muscle weakness Behavioral - ataxia Behavioral - muscle contraction or spasticity

REFERENCE :

HEPHD2 Handbook of Experimental Pharmacology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.50- 1978- Volume(issue)/page/year: 55,527,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

140 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

APPHAX Acta Poloniae Pharmaceutica. For English translation, see APPFAR. (Ars Polona, POB 1001, 00-680 Warsaw 1, Poland) V.1- 1937- Volume(issue)/page/year: 40,235,1983

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

31 mg/kg

TOXIC EFFECTS :

Behavioral - muscle weakness Behavioral - ataxia Behavioral - muscle contraction or spasticity

REFERENCE :

HEPHD2 Handbook of Experimental Pharmacology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.50- 1978- Volume(issue)/page/year: 55,527,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

5760 mg/kg/22W-I

TOXIC EFFECTS :

Cardiac - EKG changes not diagnostic of specified effects Related to Chronic Data - death

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1709,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

650 mg/kg/7W-I

TOXIC EFFECTS :

Cardiac - EKG changes not diagnostic of specified effects

REFERENCE :

ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year: 51,43,1982