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Levomepromazine

Levomepromazine structure

CAS No:
60-99-1
Formula:
C19H24N2OS
Chemical Name:
Levomepromazine
Synonyms:
10H-Phenothiazine-10-propanamine,2-methoxy-N,N,β-trimethyl-,(βR)-;Phenothiazine,10-[3-(dimethylamino)-2-methylpropyl]-2-methoxy-,(-)-;10H-Phenothiazine-10-propanamine,2-methoxy-N,N,β-trimethyl-,(R)-;(βR)-2-Methoxy-N,N,β-trimethyl-10H-phenothiazine-10-propanamine;Levomepromazine;Levopromazine;Levoprome;Levopromethazine;Nozinan;Sinogan;Mepromazine;Levomepromazin;Methotrimeprazine;Nozinane;SKF 5116;7044 R.P.;2-Methoxytrimeprazine;Levomeprazine;Sinogan-Debil;Nirvan;Tisercin;Neozine;RP 7044;CL 36467;CL 39743;Hirnamin;Levotomin;XP 03;NSC 226516;(2R)-3-(2-Methoxyphenothiazin-10-yl)-N,N,2-trimethylpropan-1-amine;704201-35-4
Categories:
Active Pharmaceutical Ingredients > Nervous System Drugs

Description

Methotrimeprazine (Levomepromazine) is an orally available neuroleptic agent, which is commonly used to relieve nausea and vomiting in palliative care settings. Levomepromazine has antagonist actions at multiple neurotransmitter receptor sites, including dopaminergic, cholinergic, serotonin and histamine receptors[1].

Solid

Methotrimeprazine is a member of the class of phenothiazines that is 10H-phenothiazine substituted by a (2R)-3-(dimethylamino)-2-methylpropyl group and a methoxy group at positions 10 and 2 respectively. It has a role as a phenothiazine antipsychotic drug, a dopaminergic antagonist, a serotonergic antagonist, a cholinergic antagonist, a non-narcotic analgesic, an EC 3.4.21.26 (prolyl oligopeptidase) inhibitor and an anticoronaviral agent. It is a member of phenothiazines and a tertiary amine. It derives from a hydride of a 10H-phenothiazine.|A phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)|Levomepromazine is a phenothiazine and typical antipsychotic agent, with sedative/hypnotic, anxiolytic, antiemetic, analgesic and antipsychotic activities. Although the exact mechanism of action of levomepromazine is not fully known, upon administration, this agent appears to act as an antagonist for a variety of receptors in the central nervous system (CNS), including adrenergic, dopamine, histamine, cholinergic and serotonin (5-hydroxytryptamine; 5-HT) receptors. Blocking these receptors results in levomepromazine's pharmacologic effects.|A phenothiazine with pharmacological activity similar to that of both CHLORPROMAZINE and PROMETHAZINE. It has the histamine-antagonist properties of the antihistamines together with CENTRAL NERVOUS SYSTEM effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)

Levomepromazine Basic Attributes

Molecular Weight：

444.54

Exact Mass：

328.47

EC Number：

200-495-5

UNII：

9G0LAW7ATQ

DSSTox ID：

DTXSID1023289

NCI Thesaurus Code：

C66118

ATC Code：

N05AA02|N - Nervous system

HScode：

2934300000

Characteristics

PSA：

41.01000

XLogP3：

4.56060

Appearance：

Solid

Density：

1.125g/cm3

Melting Point：

117°C

Boiling Point：

468ºC at 760 mmHg

Flash Point：

236.8ºC

Refractive Index：

1.594

Water Solubility：

20mg/L(25 ºC)

Toxicity：

LD50 oral in rat: 1100mg/kg

PKA：

9.19None

Dissociation Constants：

9.19

Collision Cross Section：

176.8 Å² [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

Safety Information

Packing level：

III

Hazard category：

6.1(b)

Transport codes：

3249

hazard class code：

20/21/22

safety instructions：

RTECS Number：

SO6125000

Marks：

Precautionary statement(s)：

P261-P280-P301 + P312 + P330

Hazard Statements：

H302 + H312 + H332

GHS Classification：

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P273, P280, P301+P312, P302+P352, P321, P330, P333+P313, P363, P391, and P501|Aggregated GHS information provided by 32 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, and P501|Aggregated GHS information provided by 39 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Toxicity

Toxicity Summary：

Symptoms of overdose include convulsions, spastic movements, and coma.

Drug Information

Drug Indication：

For the treatment of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder.

Pharmacology：

Methotrimeprazine is a phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)

MeSH：

A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS. (See all compounds classified as Analgesics, Non-Narcotic.)|Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME. (See all compounds classified as Dopamine Antagonists.)|Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. (See all compounds classified as Antipsychotic Agents.)

Absorption：

Methotrimeprazine has an incomplete oral bioavailability, because it undergoes considerable first-pass-metabolism in the liver. Oral bioavailability is approximately 50 to 60%.

Metabolism/Metabolites：

Hepatic. Methotrimeprazine is metabolized in the liver and degraded to a sulfoxid-, a glucuronid- and a demethyl-moiety.

Biological Half-Life：

Approximately 20 hours.

Mechanism of Action：

Methotrimeprazine's antipsychotic effect is largely due to its antagonism of dopamine receptors in the brain. In addition, its binding to 5HT2 receptors may also play a role.

MeSH Entry Terms：

Levomeprazin

Levomepromazine Use and Manufacturing

Uses

Analgesic

Use Classification：

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals

Computed Properties

Molecular Weight:328.5
XLogP3:4.7
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:328.16093457
Monoisotopic Mass:328.16093457
Topological Polar Surface Area:41
Heavy Atom Count:23
Complexity:378
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes