Mesoridazine

Mesoridazine (TPS-23) , a metabolite of Thioridazine (HY-B0965A), acts as an orally active phenothiazine antipsychotic agent. Mesoridazine is a potent and rapid open-channel blocker of human ether-a-go-go related gene (hERG) channels and blocks hERG currents with an IC50 of 550 nM (at 0 mV) in human embryonic kidney 293 cells[1].Mesoridazine can be used for the research of schizophrenia, as well as certain other psychiatric disorders[1][2].

Research Areas >> Neurological Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

IC50: hERG currents[1]

Mesoridazine blocks human ether-a-go-go-related gene (HERG) currents in a concentration-dependent manner (IC50 = 550 nM at 0 mV), block increased significantly over the voltage range where HERG activates and saturates at voltages eliciting maximal HERG channel activation[1]. Mesoridazine (15 mM; 24 h) shows total absorption of 15.94 ± 4.04% and 39.24 ± 5.11% in nude mouse and pig skin, respectively[3].

Mesoridazine (15 mM; topical administration; once or daily for 7 consecutive days) displays potent activity and a long period of analgesia at blocking cutaneous pain[3]. Mesoridazine (15 mM) shows intradermal concentration of 0.34 0.74 nmol/mg after topical application on nude mouse back for 6 h[3]. Animal Model: Eight-week-old female nude mice[3] Dosage: 15 mM Administration: Topical administration, once (analgesia test) or daily for 7 consecutive days (irritation test) Result: Showed analgesic effect. A slight transepidermal water loss (TEWL) increased from 7.8 to 9.9 g/m2/h was observed.

[1]. Zhi Su, et al. Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel. J Mol Cell Cardiol. 2004 Jan;36(1):151-60.

[2]. I S M Salih, et al. Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses. Clin Pharmacol Ther. 2007 Nov;82(5):548-54.

[3]. Liu KS, et al. Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment. Eur J Pharm Biopharm. 2016 Aug;105:59-68.

MOLECULAR FORMULA :

C21-H26-N2-O-S2

MOLECULAR WEIGHT :

386.61

WISWESSER LINE NOTATION :

T C666 BN ISJ ESO&1 B2- BT6NTJ A

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

86 mg/kg

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction)

REFERENCE :

JCPYDR Journal of Clinical Pyschopharmacology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1981- Volume(issue)/page/year: 2,222,1982

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

42 mg/kg

TOXIC EFFECTS :

Vascular - regional or general arteriolar or venous dilation Lungs, Thorax, or Respiration - chronic pulmonary edema Blood - hemorrhage

REFERENCE :

ARGPAQ Archives of General Psychiatry. (AMA, 535 N. Dearborn St., Chicago,IL 60610) V.3- 1960- Volume(issue)/page/year: 34,955,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

644 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

509 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

560 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,29,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

26 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,29,1972

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

800 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

405 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

60480 mg/kg/72W-I

TOXIC EFFECTS :

Brain and Coverings - recordings from specific areas of CNS Skin and Appendages - dermatitis, other (after systemic exposure) Related to Chronic Data - death

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4738 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 103 (estimated) No. of Female Employees: 52 (estimated)