| Revision as of 07:00, 24 October 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (changes to verified fields - updated 'ChEBI_Ref', 'CAS_number_Ref') per Chem/Drugbox validation (report errors or bugs)← Previous edit | Latest revision as of 23:36, 27 March 2024 edit undoKimen8 (talk | contribs)Extended confirmed users5,112 editsm →Pharmacology: ce caps | ||
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| {{Short description|Benzodiazepine drug}} | |||
| {{Drugbox | {{Drugbox | ||
| | Verifiedfields = changed | | Verifiedfields = changed | ||
| | Watchedfields = changed | |||
| | verifiedrevid = |
| verifiedrevid = 462101416 | ||
| | IUPAC_name = |
| IUPAC_name = 7-chloro-1-methyl-5-phenyl-2,3-dihydro-1,4-benzodiazepine | ||
| | image = Medazepam skeletal.svg | |||
| | |
| image = Medazepam.svg | ||
| | width = 170 | |||
| | image2 = Medazepam3d.png | |||
| | image2 = Medazepam ball-and-stick model.png | |||
| <!--Clinical data--> | <!--Clinical data--> | ||
| | tradename = |
| tradename = Rudotel | ||
| | Drugs.com = {{drugs.com|international|medazepam}} | | Drugs.com = {{drugs.com|international|medazepam}} | ||
| | pregnancy_category = |
| pregnancy_category = | ||
| | legal_BR = B1 | |||
| | legal_status = ](US) | |||
| | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref> | |||
| | legal_CA = Schedule IV | |||
| | legal_DE = Rx-only/Anlage III | |||
| | legal_US = Schedule IV | |||
| | routes_of_administration = Oral | | routes_of_administration = Oral | ||
| <!--Pharmacokinetic data--> | <!--Pharmacokinetic data--> | ||
| | bioavailability = |
| bioavailability = 50–75% (С<sub>max</sub> = 1–2 hours) | ||
| | protein_bound = >99% | |||
| | metabolism = ] | | metabolism = ] | ||
| | elimination_half-life = |
| elimination_half-life = 2 hours, 36–150 hours (terminal) | ||
| | excretion = ] | | excretion = ] (63–85%), ] 15–37% | ||
| <!--Identifiers--> | <!--Identifiers--> | ||
| | CAS_number_Ref = {{cascite| |
| CAS_number_Ref = {{cascite|changed|??}} | ||
| | CAS_number = 2898-12-6 | | CAS_number = 2898-12-6 | ||
| | ATC_prefix = N05 | | ATC_prefix = N05 | ||
| | ATC_suffix = BA03 | | ATC_suffix = BA03 | ||
| | PubChem = 4041 | | PubChem = 4041 | ||
| | DrugBank_Ref = {{drugbankcite| |
| DrugBank_Ref = {{drugbankcite|changed|drugbank}} | ||
| | DrugBank = none | | DrugBank = none | ||
| | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ||
| | ChemSpiderID = 3901 | | ChemSpiderID = 3901 | ||
| | UNII_Ref = {{fdacite| |
| UNII_Ref = {{fdacite|correct|FDA}} | ||
| | UNII = P0J3387W3S | | UNII = P0J3387W3S | ||
| | KEGG_Ref = {{keggcite|correct|kegg}} | | KEGG_Ref = {{keggcite|correct|kegg}} | ||
| Line 39: | Line 46: | ||
| <!--Chemical data--> | <!--Chemical data--> | ||
| | C=16 | H=15 | Cl=1 | N=2 | | C=16 | H=15 | Cl=1 | N=2 | ||
| | smiles = ClC1=CC(C(C2=CC=CC=C2)=NCCN3C)=C3C=C1 | |||
| | molecular_weight = 270.8 | |||
| | smiles = Clc3ccc1c(\C(=N/CCN1C)c2ccccc2)c3 | |||
| | InChI = 1/C16H15ClN2/c1-19-10-9-18-16(12-5-3-2-4-6-12)14-11-13(17)7-8-15(14)19/h2-8,11H,9-10H2,1H3 | |||
| | InChIKey = YLCXGBZIZBEVPZ-UHFFFAOYAU | |||
| | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | ||
| | StdInChI = 1S/C16H15ClN2/c1-19-10-9-18-16(12-5-3-2-4-6-12)14-11-13(17)7-8-15(14)19/h2-8,11H,9-10H2,1H3 | | StdInChI = 1S/C16H15ClN2/c1-19-10-9-18-16(12-5-3-2-4-6-12)14-11-13(17)7-8-15(14)19/h2-8,11H,9-10H2,1H3 | ||
| Line 49: | Line 53: | ||
| }} | }} | ||
| '''Medazepam''' is a drug that is a ] derivative. It possesses ], ], ], and ] properties. It is known by the following brand names: '''Azepamid''', '''Nobrium''', '''Tranquirax''' (mixed with ]), '''Rudotel''', '''Raporan''', '''Ansilan''' and '''Mezapam'''.<ref>{{cite encyclopedia | url = http://www.drug-encyclopedia.eu/DW_EN/benzodiazepines.shtml | encyclopedia = Encyclopedia of Drugs | title = Benzodiazepines }}</ref> Medazepam is a long-acting benzodiazepine drug. The half-life of medazepam is 36–200 hours.<ref>{{cite web | url = http://www.bcnc.org.uk/equivalence.html | date = April 2007 | title = Benzodiazepine Equivalency Table | access-date = September 23, 2007 | first = Heather | last = Ashton | name-list-style = vanc | work = Benzodiazepines Co-operation Not Confrontation (BCNC) | archive-date = September 28, 2007 | archive-url = https://web.archive.org/web/20070928121055/http://www.bcnc.org.uk/equivalence.html | url-status = dead }}</ref> | |||
| '''Medazepam''' is a drug which is a ] derivative. It possesses ], ], ] and ] properties. | |||
| It is known by the following brand names: '''Nobrium''', '''Rudotel''', '''Raporan''', '''Ansilan'''.<ref></ref> Medazepam is a long acting benzodiazepine drug. The half-life of medazepam is 36 – 200 hours.<ref>{{cite web | url = http://www.bcnc.org.uk/equivalence.html | title = BENZODIAZEPINE EQUIVALENCY TABLE | accessdate = September 23, 2007 | author = Professor heather Ashton | year = 2007 | month = April }}</ref> | |||
| ==Pharmacology== | ==Pharmacology== | ||
| Medazepam acts as a ] to ]. | |||
| Benzodiazepine drugs including medazepam increase the inhibitory processes in the cerebral cortex by allosteric modulation of the GABA receptor.<ref>{{cite journal | |
Benzodiazepine drugs including medazepam increase the inhibitory processes in the cerebral cortex by allosteric modulation of the GABA receptor.<ref>{{cite journal | vauthors = Zakusov VV, Ostrovskaya RU, Kozhechkin SN, Markovich VV, Molodavkin GM, Voronina TA | title = Further evidence for GABA-ergic mechanisms in the action of benzodiazepines | journal = Archives Internationales de Pharmacodynamie et de Therapie | volume = 229 | issue = 2 | pages = 313–26 | date = October 1977 | pmid = 23084 }}</ref> Benzodiazepines may also act via ] benzodiazepine-binding sites as ] channel blockers and significantly inhibited depolarization-sensitive calcium uptake in experiments with cell components from rat brains. This has been conjectured as a mechanism for high dose effects against seizures in a study.<ref>{{cite journal | vauthors = Taft WC, DeLorenzo RJ | title = Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 10 | pages = 3118–22 | date = May 1984 | pmid = 6328498 | pmc = 345232 | doi = 10.1073/pnas.81.10.3118 | url = http://www.pnas.org/cgi/reprint/81/10/3118.pdf | type = PDF | bibcode = 1984PNAS...81.3118T | doi-access = free }}</ref> It has major active benzodiazepine metabolites, which gives it a more prolonged therapeutic effect after administration.<ref>{{cite journal | vauthors = Jochemsen R, Breimer DD | title = Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles | journal = Current Medical Research and Opinion | volume = 8 Suppl 4 | pages = 60–79 | year = 1984 | pmid = 6144464 | doi = 10.1185/03007998409109545 }}</ref> | ||
| ⚫ | == See also == | ||
| ==The Committee on the Review of Medicines== | |||
| The Committee on the Review of Medicines (UK) carried out a review into benzodiazepines due to significant concerns of tolerance, ] and ] problems and other adverse effects. The committee found that benzodiazepines do not have any ] or ] properties and are therefore unsuitable treatments for conditions such as depression, ] and ]. Benzodiazepines are also not beneficial in the treatment of ] due to a lack of efficacy. The committee also recommended against benzodiazepines being used in the treatment of ] or ] in children. The committee was in agreement with the ] (USA) and the conclusions of a study carried out by the ] and the ] (USA) that there was little evidence that long term use of benzodiazepine hypnotics were benefitial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep promoting properties within 3 – 14 days of continuous use and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months continuous use due to the development of tolerance. The committee found that the regular use of benzodiazepines caused the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the ] including symptoms such as ], ], ], ], ], and ] upon cessation of benzodiazepine use. Withdrawal symptoms tended to develop within 24 hours on the cessation of a short acting benzodiazepine and within 3 – 10 days after the cessation of a more long acting benzodiazepine. Withdrawal effects could occur after treatment lasting only 2 weeks at therapeutic dose levels however withdrawal effects tended to occur with habitual use beyond 2 weeks and were more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition. The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short term use only. It was noted in the review that alcohol can potentiate the ] depressant effects of benzodiazepines and should be avoided. The central nervous system depressant effects of benzodiazepines may make driving or operating machinery dangerous and the elderly are more prone to these adverse effects. In the ] high single doses or repeated low doses have been reported to produce ], poor sucking, and ] in the ] and irregularities in the ] heart. Benzodiazepines should be avoided in ]. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause ], ], ], or a condition resembling ]. Abrupt withdrawal from lower doses may cause depression, ], ], ], ], and ].<ref>{{cite journal | author = Committee on the Review of Medicines | date = March 29, 1980 | title = Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines | journal = Br Med J. | volume = 280 | issue = 6218 | pages = 910–2 | pmid = 7388368 | doi = 10.1136/bmj.280.6218.910 | pmc = 1601049 }}</ref> | |||
| ==Chemistry== | |||
| 7-chloro-2,3-dihydro-1-methyl-5-phenyl-1H-1,4-benzodiazepine | |||
| (5.1.40), has been suggested to be synthesized in various ways. The first is the | |||
| reduction of the carbonyl group in diazepam by ]. | |||
| *{{Cite doi|10.1021/jo01044a514}} | |||
| *E. Reeder, L.H. Sternbach, {{US Patent|3109843}} (1963). | |||
| ] | |||
| The second way of making medazepam consists of the initial reduction of the ] | |||
| group by ] into 7-chloro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin- | |||
| 2-one—the first intermediate product in the synthesis of diazepam—which is synthesized by the cyclocondensation of 2-amino-5-chlorobenzophenone with ] ethyl ester into 7-chloro-2,3-dihydro-5-phenyl-1H-1,4-benzodiazepine, and the subsequent methylation of the secondary amine nitrogen atom of the resulting product by ], using ] as a base. | |||
| *S. Inaba, H. Nagata, {{Cite patent|DE|1934385}} (1971). | |||
| *G.A. Archer, E. Fells, L.H. Sternbach, {{US Patent|3131178}} (1964). | |||
| ] | |||
| The third method of making medazepam consists of a new way of making 7-chloro-2,3- | |||
| dihydro-5-phenyl-1H-1,4-benzodiazepine, which consists in heterocyclization of | |||
| 1-(2,5-dichlorophenyl)-1-phenylimine with ]. The starting 1-(2,5- | |||
| dichlorophenyl)-1-phenylimine is synthesized by the reaction of 2,5-dichlorobenzonitrile | |||
| with ]. | |||
| *S. Inaba, H.Nagata, {{Cite patent|DE|1934385}} (1969). | |||
| ] | |||
| Finally, a method of making medazepam from 4-chloro-N-methylaniline is suggested. The | |||
| last is reacted with ethyleneimine in the presence of ], giving N- | |||
| (4-chlorophenyl)-N-methylethylenediamine. ] of the resulting product | |||
| with ] gives the respective ], which cyclizes into the desired | |||
| medazepam using ]. | |||
| *K.H. Heinrich, {{Cite patent|DE|1695188}} (1967). | |||
| *K.H. Heinrich, {{Cite patent|DE|1795811}} (1967). | |||
| ] | |||
| See also: | |||
| *Wunsch, K. H.; Dettmann, H.; Schonberg, S.; Chem. Ber. 1969, 102, 3891. | |||
| ] | |||
| Various modifications of the described methods have been suggested. | |||
| *S. Inaba, K. Ishizumi, T. Okamoto, H. Yamamoto, Chem. Pharm. Bull., 20, 1628 (1972). | |||
| *M. Mihalic, V. Sunjic, F. Kajfez, M. Zinic, J. Heterocycl. Chem., 14, 941 (1977). | |||
| ⚫ | ==See also== | ||
| *] | |||
| *] | *] | ||
| *] | *] | ||
| *] | *] | ||
| ==References== | == References == | ||
| {{reflist}} | |||
| <references/> | |||
| ==External links== | == External links == | ||
| * | * | ||
| {{Benzodiazepines}} | {{Benzodiazepines}} | ||
| {{Anxiolytics}} | {{Anxiolytics}} | ||
| {{GABAAR PAMs}} | |||
| ] | ] | ||
| ] | ] | ||
| ] | |||
| ] | |||
| ] | |||
| ] | |||
| ] | |||
| ] | |||
Latest revision as of 23:36, 27 March 2024
Benzodiazepine drug Pharmaceutical compound | |
 | |
| Clinical data | |
|---|---|
| Trade names | Rudotel |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Oral |
| ATC code | |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | 50–75% (Сmax = 1–2 hours) |
| Protein binding | >99% |
| Metabolism | Hepatic |
| Elimination half-life | 2 hours, 36–150 hours (terminal) |
| Excretion | Renal (63–85%), Biliary 15–37% |
| Identifiers | |
IUPAC name
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.018.895  |
| Chemical and physical data | |
| Formula | C16H15ClN2 |
| Molar mass | 270.76 g·mol |
| 3D model (JSmol) | |
SMILES
| |
InChI
| |
| (what is this?) (verify) | |
Medazepam is a drug that is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative, and skeletal muscle relaxant properties. It is known by the following brand names: Azepamid, Nobrium, Tranquirax (mixed with bevonium), Rudotel, Raporan, Ansilan and Mezapam. Medazepam is a long-acting benzodiazepine drug. The half-life of medazepam is 36–200 hours.
Pharmacology
Medazepam acts as a prodrug to nordazepam. Benzodiazepine drugs including medazepam increase the inhibitory processes in the cerebral cortex by allosteric modulation of the GABA receptor. Benzodiazepines may also act via micromolar benzodiazepine-binding sites as Ca channel blockers and significantly inhibited depolarization-sensitive calcium uptake in experiments with cell components from rat brains. This has been conjectured as a mechanism for high dose effects against seizures in a study. It has major active benzodiazepine metabolites, which gives it a more prolonged therapeutic effect after administration.
See also
References
- Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
- "Benzodiazepines". Encyclopedia of Drugs.
- Ashton H (April 2007). "Benzodiazepine Equivalency Table". Benzodiazepines Co-operation Not Confrontation (BCNC). Archived from the original on September 28, 2007. Retrieved September 23, 2007.
- Zakusov VV, Ostrovskaya RU, Kozhechkin SN, Markovich VV, Molodavkin GM, Voronina TA (October 1977). "Further evidence for GABA-ergic mechanisms in the action of benzodiazepines". Archives Internationales de Pharmacodynamie et de Therapie. 229 (2): 313–26. PMID 23084.
- Taft WC, DeLorenzo RJ (May 1984). "Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations" (PDF). Proceedings of the National Academy of Sciences of the United States of America (PDF). 81 (10): 3118–22. Bibcode:1984PNAS...81.3118T. doi:10.1073/pnas.81.10.3118. PMC 345232. PMID 6328498.
- Jochemsen R, Breimer DD (1984). "Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles". Current Medical Research and Opinion. 8 Suppl 4: 60–79. doi:10.1185/03007998409109545. PMID 6144464.