Mianserin hydrochloride

Mianserin hydrochloride is a H1 receptor inverse agonist and is a psychoactive agent of the tetracyclic antidepressant.Target: H1 receptorMianserin is a psychoactive drug of the tetracyclic antidepressant (TeCA) therapeutic family. It is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA) and has antidepressant, anxiolytic (anti-anxiety), hypnotic (sedating), antiemetic (nausea and vomiting-attenuating), orexigenic (appetite-stimulating), and antihistamine effects. It is not approved for use in the US, but its analogue, mirtazapine, is. Mianserin was the first antidepressant to reach the UK market that was less dangerous than the tricyclic antidepressants in overdose.Mianserin is an antagonist/inverse agonist of the H1, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, and α2-adrenergic receptors, and also inhibits the reuptake of norepinephrine. As a high affinity H1 receptor inverse agonist, mianserin has strong antihistamine effects (sedation, weight gain, etc.). Contrarily, it has negligible affinity for the mACh receptors, and thus lacks any anticholinergic properties. It was recently found to be a potent kappa opioid receptor agonist. In addition, mianserin also appears to be a potent antagonist of the neuronal octopamine receptor. What implications this may have on mood are currently unknown, however octopamine has been implicated in the regulation of sleep, appetite and insulin production and therefore may theoretically contribute to the overall side effect profile of mianserin.

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Natural Products >> Alkaloid

Research Areas >> Neurological Disease

[1]. Olianas MC,et al. The atypical antidepressant mianserin exhibits agonist activity at κ-opioid receptors. Br J Pharmacol. 2012 Nov;167(6):1329-41.

[2]. Roeder T. High-affinity antagonists of the locust neuronal octopamine receptor. Eur J Pharmacol. 1990 Nov 27;191(2):221-4.

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MOLECULAR FORMULA :

C18-H20-N2.Cl-H

MOLECULAR WEIGHT :

300.86

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

28 mg/kg/5W

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Cardiac - change in rate Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

18 mg/kg

TOXIC EFFECTS :

Behavioral - coma Cardiac - pulse rate Cardiac - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

780 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

262 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>3 gm/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

31850 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

224 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

117 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

118 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Skin and Appendages - hair

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 - tremor Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Gastrointestinal - ulceration or bleeding from small intestine Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 mg/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

MUTATION DATA

TEST SYSTEM :

Insect - Drosophila melanogaster

DOSE/DURATION :

100 mmol/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 286,155,1993