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Levomepromazine
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| Systematic (IUPAC) name | |
| (2R)-3-(2-Methoxyphenothiazine-10-yl-)-N,N,2-trimethylpropanamine | |
| Identifiers | |
| CAS number | (7104-38-3 [maleate], 1236-99-3 [HCl]) |
| ATC code | N05 |
| PubChem | |
| Chemical data | |
| Formula | C19H24N2OS |
| Mol. mass | 328. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the Sulfur or sulphur (ˈsʌlfɚ see spelling below) is the Chemical element that has the Atomic number 16 The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 473 g/mol |
| Pharmacokinetic data | |
| Bioavailability | approx. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of 50 to 60% |
| Metabolism | Hepatic |
| Half life | ~ 20 hours |
| Excretion | feces and urine (metabolites), unchanged drug only 1% |
| Therapeutic considerations | |
| Pregnancy cat. |
Only if clearly needed |
| Legal status |
Rx-only (n. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction a. in the USA) |
| Routes | oral, seldom i. In Pharmacology and Toxicology, a route m. |
Contents |
General Remarks and Pharmacology
Levomepromazine in Germany and Methotrimeprazine in America (Sold as Nosinan Nozinan, Levoprome) is an aliphatic phenothiazine neuroleptic drug. In Organic chemistry, compounds composed of Carbon and Hydrogen are divided into two classes Aromatic compounds which contain Benzene rings Phenothiazine is the Organic compound with the formula S(C6H42NH Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease It is a low potent antipsychotic (approximately half as potent as chlorpromazine). Chlorpromazine (as chlorpromazine Hydrochloride, abbreviated CPZ, marketed in the US as Thorazine) is a Phenothiazine Antipsychotic It has strong analgesic and also strong antiemetic properties. An anti-emetic is a drug that is effective against Vomiting and Nausea. Serious side effects include tardive dyskinesia and the potentially fatal neuroleptic malignant syndrome. Tardive dyskinesia is a variety of dyskinesia (involuntary repetitive movements manifesting as a side effect of long-term or high-dose use of Dopamine antagonists Neuroleptic malignant syndrome (NMS is a life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs. Patient willingness to take this drug is low because of the agonizing side effect of akathisia. Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of "inner" restlessness that manifests itself with an inability to sit still or remain It is an aliphatic compound combined with phenothiazine which was introduced by Dupont as an insecticide in 1935. In Organic chemistry, compounds composed of Carbon and Hydrogen are divided into two classes Aromatic compounds which contain Benzene rings Phenothiazine is the Organic compound with the formula S(C6H42NH It exerts its actions through a central adrenergic-blocking, a dopamine-blocking, a serotonin-blocking, and a anticholinergic blocking. Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine [1]
- Absorption, and other characteristics : Levomepromazine has an incomplete oral bioavailability, because it undergoes considerable first-pass-metabolism in the liver. It has a halflife of approximately 20 hours (15 to 30 hours). Maximum plasma levels are reached 1 to 4 hours after oral dosing. After i. m. -doses maximum plasma levels are seen after 30 to 90 minutes.
- Distribution : The approximate distribution volume is 30 l/kg. Levomepromazin is lipophilic and crosses easily the blood-brain-barrier and the placenta, and can also be found in the milk of breast-feeding mothers. Liquor concentration usually exceeds the plasma concentrations.
- Metabolism : Levomepromazine is metabolized in the liver and degraded to a Sulfoxid-, a Glucuronid- and a Demethyl-moiety.
- Elimination : Drug elimination (as metabolites, only 1% of unchanged levomepromazin is recovered) is relatively slow. The metabolites are found in feces and urine.
- Mode of Action : Levomepromazine blocks the following postsynaptic receptors:
The mode of action explains the particular pharmacological effects of levomepromazine. An acetylcholine receptor (abbreviated AChR) is an Integral membrane protein that responds to the binding of the Neurotransmitter Acetylcholine The alpha-1 adrenergic receptor (α1-AR is an Adrenergic receptor with the primary effect of Vasoconstriction. In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also The H1 receptor is a Histamine receptor, and thus an important target for clinically important drugs and is likely one of the most important receptors for modulating Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the Vertebrate Central nervous system (CNS Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the Vertebrate Central nervous system (CNS Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the Vertebrate Central nervous system (CNS The α2 receptor is a type of Adrenergic receptor. Effect The α2 receptor has several general functions in common with other α-receptors but also In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also
Currently, levomepromazine is not registered in the USA. In Europe it has been marketed for decades as Neurocil and Nozinan. Nozinan is also available in Canada.
Some American physicians are currently conducting studies regarding the strong analgesic effect of levomepromazine.
Indications
Levomepromazine is used for the treatment of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder. Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn Mania (from Greek μανία and that from μαίνομαι - mainomai, "to rage to be furious" is a severe medical condition It should never be used in the treatment of agitated depressions because this drug increases agitation through the side effect of akathisia. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of "inner" restlessness that manifests itself with an inability to sit still or remain
Levomepromazine is also used at lower doses for the treatment of Nausea. Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort
Side effects
The most commonly complained about side effect is the agonizing akathisia. Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of "inner" restlessness that manifests itself with an inability to sit still or remain Levomepromazine has prominent sedative and anticholinergic/sympatholytic effects (dry mouth, hypotension, sinus tachycardia, extreme night sweats) and causes massive weight gain. A sedative, or more specifically a sedative-hypnotic, is a substance that depresses the Central nervous system (CNS resulting in calmness relaxation sleepiness An anticholinergic agent is a substance that blocks the Neurotransmitter acetylcholine in the central and the Peripheral nervous system. A sympatholytic drug is a medication which inhibits the Postganglionic functioning of the Sympathetic nervous system (SNS In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. Sinus Tachycardia (also colloquially known as sinus tach or sinus tachy) is a rhythm with elevated rate of impulses originating from the Sinoatrial These side effects normally preclude prescribing the drug in doses needed for full remission of schizophrenia, so it has to be combined with a more potent antipsychotic. Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. In any case, blood pressure and EKG should be monitored regularly.
Other symptoms include muscle stiffness, fever and neuroleptic malignant syndrome. Neuroleptic malignant syndrome (NMS is a life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs.
Interactions
Dosages of concomitantly administered opioids should be reduced by approximately half, because levomepromazine amplifies the therapeutic actions and side-effects of opioids. An opioid is a chemical Substance that has a Morphine -like action in the body Combination with tramadol (Ultram) is associated with increased risk of seizures. Tramadol ( INN) (ˈtræmədɒl is an atypical Opioid which is a centrally acting Analgesic, used for treating moderate to severe Pain. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting
Additive sedative effects and confusional states may emerge if levomepromazine is given with benzodiazepines or barbiturates. This may be avoided by using the lowest dose possible with the substances in question.
Exert particular caution in combining levomepromazine with other anticholinergic drugs (tricyclic antidepressants and antiparkinsonian-agents): Particularly the elderly may develop delirium, high fever, severe obstipation, even ileus and glaucoma. Ileus is a disruption of the normal propulsive gastrointestinal motor activity from non-mechanical mechanisms Glaucoma is a group of diseases of the Optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. Reduce both the dose of levomepromazine and the dose of the other drug. If possible, avoid such combinations.
Caffeine and/or stimulantes of the ephedrine/amphetamine type may counteract the specific actions of levomepromazine. Concomitant use of these substances should be avoided.
Coffee and black tea should be avoided because they decrease the absorption of levomepromazine considerably. The same is true for antacids; these should be given 1 to 2 hours before or after oral administration of leveomepromazine.
References
- ^ "Facts and Comparisons" III W. Port Plaza, Suite 300 St. Louis MO. USA 63146-3098 (telephone 314-216-2100 or 1-800-223-0554). (Note this book is currently used by Rite Aid Pharmacies in the USA as a reference aid and it is a loose bound updatable book. The updatable section called "Antipsychotic Agents" is (c)1990
- PubChem Substance Summary: Levomepromazine National Center for Biotechnology Information.
- NOZINAN - Lévomépromazine Doctissimo Guides des Medicaments
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