Moclobemide

Structural formula
General
Non-proprietary name	Moclobemide
other names	4-chloro- N - (2-morpholino-ethyl) benzamide ( IUPAC )
Molecular formula	C 13 H 17 ClN 2 O 2
Brief description	white to yellowish white or reddish white, polymorphic powder
External identifiers / databases
CAS number 71320-77-9 EC number 636-108-5 ECHA InfoCard 100.163.935 PubChem 4235 DrugBank DB01171 Wikidata Q421934
Drug information
ATC code	N06 AG02
Drug class	Antidepressants
Mechanism of action	reversible inhibition of monoamine oxidase type A.
properties
Molar mass	268.74 g · mol -1
Melting point	137 ° C (free base) 208 ° C ( hydrochloride )
solubility	slightly soluble in water, slightly soluble in dichloromethane and ethanol 96%
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 302-315-318-335 P: 261-280-305 + 351 + 338
Toxicological data	707 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Moclobemid , systematic name 4-chloro- N - (2-morpholinoethyl) benzamide , is a crystalline substance that occurs not only as a free base but also as a hydrochloride . Moclobemid is a substituted benzamide that is structurally related to sulpiride and remoxiprid .

Indications

The indication for the use of moclobemide are depressive syndromes . Since moclobemide does not have a sedating effect, it is suitable for the treatment of inhibited depression , but not in agitated or suicidal patients. It is also approved in Germany for the treatment of social phobia .

Effects

Moclobemide is a largely selective, reversible inhibitor of monoamine oxidase A, which reversibly inhibits monoamine oxidase B by about 30% (estimate based on the noradrenaline breakdown products MHPG and DHPG with daily administration of 600 mg moclobemide, MAO-A inhibition about 50%). This causes a lower metabolism of the neurotransmitters serotonin and norepinephrine , their concentration increases, which leads to an improvement of mood and drive in depression. Since tyramine displaces moclobemide from its binding to MAO A (reversibility), hypertensive crises do not occur with moclobemide when tyramine is taken in with food, unlike irreversible MAO inhibitors (e.g. tranylcypromine ). According to the manufacturer, there are therefore no special dietary requirements to be observed. Moclobemide is non-sedating and hardly anticholinergic . In clinical studies, the effectiveness was comparable to that of tricyclic antidepressants, with mostly better tolerability. It is advantageous that moclobemide has a wide therapeutic range .

dosage

The initial daily dose of 300–450 mg is divided into several individual doses; the daily dose can be reduced later. The maximum dosage is 600 mg.

Pharmacokinetics

After oral administration, moclobemide is almost completely absorbed from the gastrointestinal tract; due to a first-pass effect , the bioavailability is 50–80%. The systematic bioavailability is higher after multiple applications (80%) than after a single dose (60%). Maximum plasma concentrations are reached within one hour. The plasma protein binding is rather low at around 50%. The volume of distribution of moclobemide is 1.2 l / kg due to its lipophilic properties. Moclobemide is almost completely metabolized; the metabolites are excreted via the kidneys . The elimination half-life is between one and four hours. It increases with higher doses due to saturation of the metabolic pathways. Moclobemide is metabolized via the cytochrome P450-2C19 isoenzyme , among other things .

Impaired renal function does not require a dose adjustment; however, in the event of liver failure, the dose must be reduced because of the reduced first-pass effect.

unwanted effects

Transient insomnia , dizziness , nausea , dry mouth and headache have been observed. In very rare cases, confusion, restlessness and excitement occurred, which disappeared again after discontinuation. Skin reactions have rarely been observed, hypersensitivity reactions very rarely, often with edema formation or dyspnoea , and paresthesias have been described in isolated cases. A slight increase in plasma prolactin is possible.

Interactions

A combination with pethidine , selegiline or dextromethorphan should not be used. The combination with dextromethorphan can lead to severe disorders of the nervous system. In combination with serotonergic drugs, hyperthermia , confusion, hyperreflexia or myoclonus can occur in individual cases . Since cimetidine delays the metabolism of moclobemide and thus enhances its effect, a dose reduction of moclobemide to 30–50% is necessary when used at the same time. Opioids such as tramadol or pethidine are also enhanced in their effect by moclobemide and must therefore not be used at the same time. Although interactions with tyramine are not to be expected under normal conditions, patients with high blood pressure are advised as a precautionary measure to refrain from consuming large amounts of foods particularly rich in tyramine.

Contraindications

Since moclobemide has no sedating properties, depressed patients whose main characteristic is agitation or excitement should not receive the preparation or only receive it in combination with a sedative . It should not be used on people with states of confusion. Caution is advised in patients with thyrotoxicosis or pheochromocytoma because of the potential for triggering hypertensive reactions. In the absence of experience, treatment of children or during pregnancy and breastfeeding should also be avoided or the possible risks for the unborn child should be carefully considered.

Suicidal patients should be carefully monitored at the start of treatment.

Effects on ability to drive and use machines

As dizziness, headaches and, very rarely, seizures can occur, the ability to drive and use tools and machines may be impaired.

Finished medicinal products

Amira , Aurorix  (D, CH), Clobemix , Depnil , Manerix

Individual evidence

1. ↑ ^{a b} European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.
2. ↑ ^{a b} The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 1075, ISBN 978-0-911910-00-1 .
3. ↑ ^{a b} Moclobemide data sheet from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).
4. ↑ Entry on moclobemide in the ChemIDplus database of the United States National Library of Medicine (NLM) .
5. ↑ R. Zimmer: Relationship between tyramine potentiation and monoamine oxidase (MAO) inhibition: comparison between moclobemide and other MAO inhibitors . In: Acta psychiatrica Scandinavica. Supplement . Volume 82, No. 360, September 1990, pp. 81-83. doi : 10.1111 / j.1600-0447.1990.tb05342.x . PMID 2248084 .
6. ↑ Otto Benkert: Compendium of Psychiatric Pharmacotherapy . Ed .: Hanns Hippius. 12th edition. Springer Medizin Verlag, Heidelberg 2019, ISBN 978-3-662-57333-4 .
7. ↑ Information for professionals Moclobemid-ratiopharm (R), information as of April 2014
8. ↑ Specialist information of the Swiss Medicines Compendium: Aurorix®; Information as of March 2003.

Web links

• Critical evaluation
• drugbase.de

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