tetrazepam

Tetrazepam is used therapeutically as a muscle relaxant.{{cite journal | vauthors = Simiand J, Keane PE, Biziere K, Soubrie P | title = Comparative study in mice of tetrazepam and other centrally active skeletal muscle relaxants | journal = Archives Internationales de Pharmacodynamie et de Therapie | volume = 297 | pages = 272–85 | date = January 1989 | pmid = 2567153 }}{{cite journal | vauthors = Perez-Guerrero C, Herrera MD, Marhuenda E | title = Relaxant effect of tetrazepam on rat uterine smooth muscle: role of calcium movement | journal = The Journal of Pharmacy and Pharmacology | volume = 48 | issue = 11 | pages = 1169–73 | date = November 1996 | pmid = 8961167 | doi = 10.1111/j.2042-7158.1996.tb03915.x | s2cid = 38144317 }}

The indicated adult dose for muscle spasm is 25 mg to 150 mg per day, increased if necessary to a maximum of 300 mg per day, in divided doses. Tetrazepam is not generally recommended for use in children, except on the advice of a specialist.

Tetrazepam is only available in one strength and formulation, 50 mg tablets. The benzodiazepine equivalent of tetrazepam is approximately 100 mg of tetrazepam = 10 mg of diazepam.{{cite web| url=http://www.non-benzodiazepines.org.uk/benzodiazepine-names.html| title=Benzodiazepine Names| access-date=2009-04-05| publisher=non-benzodiazepines.org.uk| url-status=dead| archive-url=https://web.archive.org/web/20081208054743/http://www.non-benzodiazepines.org.uk/benzodiazepine-names.html| archive-date=2008-12-08}}

Allergic reactions to tetrazepam occasionally occur involving the skin.

Allergic reactions can develop to tetrazepam{{cite journal | vauthors = Camarasa JG, Serra-Baldrich E | title = Tetrazepam allergy detected by patch test | journal = Contact Dermatitis | volume = 22 | issue = 4 | pages = 246 | date = April 1990 | pmid = 2140761 | doi = 10.1111/j.1600-0536.1990.tb01587.x | s2cid = 26973793 }}{{cite journal | vauthors = Collet E, Dalac S, Morvan C, Sgro C, Lambert D | title = Tetrazepam allergy once more detected by patch test | journal = Contact Dermatitis | volume = 26 | issue = 4 | pages = 281 | date = April 1992 | pmid = 1356710 | doi = 10.1111/j.1600-0536.1992.tb00259.x | s2cid = 43750783 }} and it is considered to be a potential allergen.{{cite journal | vauthors = Ortiz-Frutos FJ, Alonso J, Hergueta JP, Quintana I, Iglesias L | title = Tetrazepam: an allergen with several clinical expressions | journal = Contact Dermatitis | volume = 33 | issue = 1 | pages = 63–5 | date = July 1995 | pmid = 7493477 | doi = 10.1111/j.1600-0536.1995.tb00462.x | s2cid = 41533643 }}{{cite journal | vauthors = Del Pozo MD, Blasco A, Lobera T | title = Tetrazepam allergy | journal = Allergy | volume = 54 | issue = 11 | pages = 1226–7 | date = November 1999 | pmid = 10604563 | doi = 10.1034/j.1398-9995.1999.00362.x | s2cid = 46139378 }} Drug rash and drug-induced eosinophilia with systemic symptoms is a known complication of tetrazepam exposure.{{cite journal | vauthors = Dinić-Uzurov V, Lalosević V, Milosević I, Urosević I, Lalosević D, Popović S | title = [Current differential diagnosis of hypereosinophilic syndrome] | journal = Medicinski Pregled | volume = 60 | issue = 11–12 | pages = 581–6 | date = November 2007 | pmid = 18666600 | doi = 10.2298/MPNS0712581D }}{{cite journal | vauthors = Bachmeyer C, Assier H, Roujeau JC, Blum L | title = Probable drug rash with eosinophilia and systemic symptoms syndrome related to tetrazepam | journal = Journal of the European Academy of Dermatology and Venereology | volume = 22 | issue = 7 | pages = 887–9 | date = July 2008 | pmid = 18031497 | doi = 10.1111/j.1468-3083.2007.02490.x | s2cid = 12775035 }} These hypersensitive allergic reactions can be of the delayed type.{{cite journal | vauthors = Blanco R, Díez-Gómez ML, Gala G, Quirce S | title = Delayed hypersensitivity to tetrazepam | journal = Allergy | volume = 52 | issue = 11 | pages = 1146–7 | date = November 1997 | pmid = 9404574 | doi = 10.1111/j.1398-9995.1997.tb00194.x | s2cid = 5381089 }}{{cite journal | vauthors = Ortega NR, Barranco P, López Serrano C, Romualdo L, Mora C | title = Delayed cell-mediated hypersensitivity to tetrazepam | journal = Contact Dermatitis | volume = 34 | issue = 2 | pages = 139 | date = February 1996 | pmid = 8681544 | doi = 10.1111/j.1600-0536.1996.tb02147.x | s2cid = 46147524 }}{{cite journal | vauthors = Kämpgen E, Bürger T, Bröcker EB, Klein CE | title = Cross-reactive type IV hypersensitivity reactions to benzodiazepines revealed by patch testing | journal = Contact Dermatitis | volume = 33 | issue = 5 | pages = 356–7 | date = November 1995 | pmid = 8565501 | doi = 10.1111/j.1600-0536.1995.tb02060.x | s2cid = 23398517 }}

Toxic epidermal necrolysis has occurred from the use of tetrazepam{{cite journal | vauthors = Delesalle F, Carpentier O, Guatier S, Delaporte E | title = Toxic epidermal necrolysis caused by tetrazepam | journal = International Journal of Dermatology | volume = 45 | issue = 4 | pages = 480 | date = April 2006 | pmid = 16650186 | doi = 10.1111/j.1365-4632.2006.02654.x | s2cid = 221815580 }}{{cite journal | vauthors = Wolf R, Orion E, Davidovici B | title = Toxic epidermal necrolysis caused by tetrazepam | journal = International Journal of Dermatology | volume = 45 | issue = 10 | pages = 1260–1 | date = October 2006 | pmid = 17040464 | doi = 10.1111/j.1365-4632.2006.03061.x | s2cid = 221815889 }} including at least one reported death.{{cite journal | vauthors = Lagnaoui R, Ramanampamonjy R, Julliac B, Haramburu F, Ticolat R | title = [Fatal toxic epidermal necrolysis associated with tetrazepam | journal = Therapie | volume = 56 | issue = 2 | pages = 187–8 | date = March 2001 | pmid = 11471372 }} Stevens–Johnson syndrome and erythema multiforme has been reported from use of tetrazepam. Cross-reactivity with other benzodiazepines does not typically occur in such patients.{{cite journal | vauthors = Pirker C, Misic A, Brinkmeier T, Frosch PJ | title = Tetrazepam drug sensitivity -- usefulness of the patch test | journal = Contact Dermatitis | volume = 47 | issue = 3 | pages = 135–8 | date = September 2002 | pmid = 12492544 | doi = 10.1034/j.1600-0536.2002.470302.x | s2cid = 5932398 }}{{cite journal | vauthors = Sánchez I, García-Abujeta JL, Fernández L, Rodríguez F, Quiñones D, Duque S, López R, Jerez J | title = Stevens-Johnson syndrome from tetrazepam | journal = Allergologia et Immunopathologia | volume = 26 | issue = 2 | pages = 55–7 | date = 2 March 1998 | pmid = 9645262 | url = http://www.elsevier.es/revistas/ctl_servlet?_f=7064&ip=90.216.52.234&articuloid=13011386&revistaid=105 | access-date = 14 September 2009 | archive-date = 25 November 2020 | archive-url = https://web.archive.org/web/20201125091827/https://www.elsevier.es/revistas/ctl_servlet?_f=7064&ip=90.216.52.234&articuloid=13011386&revistaid=105 | url-status = dead }}{{cite journal | vauthors = Rodríguez Vázquez M, Ortiz de Frutos J, del Río Reyes R, Iglesias Díez L | title = [Erythema multiforme by tetrazepam] | journal = Medicina Clinica | volume = 115 | issue = 9 | pages = 359 | date = September 2000 | pmid = 11093904 | doi = 10.1016/s0025-7753(00)71559-4 }} Exanthema{{cite journal | vauthors = Ghislain PD, Roussel S, Bouffioux B, Delescluse J | title = [Tetrazepam (Myolastan)-induced exanthema: positive patch tests in 2 cases] | journal = Annales de Dermatologie et de Vénéréologie | volume = 127 | issue = 12 | pages = 1094–6 | date = December 2000 | pmid = 11173688 }} and eczema may occur.{{cite journal | vauthors = Breuer K, Worm M, Skudlik C, Schröder C, John SM | title = Occupational airborne contact allergy to tetrazepam in a geriatric nurse | journal = Journal of the German Society of Dermatology | volume = 7 | issue = 10 | pages = 896–8 | date = October 2009 | pmid = 19453384 | doi = 10.1111/j.1610-0387.2009.07096.x | s2cid = 29339528 }} The lack of cross-reactivity with other benzodiazepines is believed to be due to the molecular structure of tetrazepam.{{cite journal | vauthors = Barbaud A, Girault PY, Schmutz JL, Weber-Muller F, Trechot P | title = No cross-reactions between tetrazepam and other benzodiazepines: a possible chemical explanation | journal = Contact Dermatitis | volume = 61 | issue = 1 | pages = 53–6 | date = July 2009 | pmid = 19659970 | doi = 10.1111/j.1600-0536.2009.01558.x | s2cid = 205813960 }}{{cite journal | vauthors = Cabrerizo Ballesteros S, Méndez Alcalde JD, Sánchez Alonso A | title = Erythema multiforme to tetrazepam | journal = Journal of Investigational Allergology & Clinical Immunology | volume = 17 | issue = 3 | pages = 205–6 | year = 2007 | pmid = 17583114 | url = http://www.jiaci.org/issues/vol17issue03/14to17.pdf }} Photodermatitis{{cite journal | vauthors = Quiñones D, Sanchez I, Alonso S, Garcia-Abujeta JL, Fernandez L, Rodriguez F, Martin-Gil D, Jerez J | title = Photodermatitis from tetrazepam | journal = Contact Dermatitis | volume = 39 | issue = 2 | pages = 84 | date = August 1998 | pmid = 9746190 | doi = 10.1111/j.1600-0536.1998.tb05840.x | s2cid = 40771488 }} and phototoxicity have also been reported.{{cite journal | vauthors = Schwedler S, Mempel M, Schmidt T, Abeck D, Ring J | title = Phototoxicity to tetrazepam - A new adverse reaction | journal = Dermatology | volume = 197 | issue = 2 | pages = 193–4 | year = 1998 | pmid = 9840980 }} Occupational contact allergy can also develop from regularly handling tetrazepam.{{cite journal | vauthors = Choquet-Kastylevsky G, Testud F, Chalmet P, Lecuyer-Kudela S, Descotes J | title = Occupational contact allergy to tetrazepam | journal = Contact Dermatitis | volume = 44 | issue = 6 | pages = 372 | date = June 2001 | pmid = 11417526 | doi = 10.1034/j.1600-0536.2001.440609-7.x }}{{cite journal | vauthors = Lepp U, Zabel P, Greinert U | title = Occupational airborne contact allergy to tetrazepam | journal = Contact Dermatitis | volume = 49 | issue = 5 | pages = 260–1 | date = November 2003 | pmid = 14996051 | doi = 10.1111/j.0105-1873.2003.0225c.x | s2cid = 11238687 }} Airborne contact dermatitis can also occur as an allergy which can develop from occupational exposure.{{cite journal | vauthors = Ferran M, Giménez-Arnau A, Luque S, Berenguer N, Iglesias M, Pujol RM | title = Occupational airborne contact dermatitis from sporadic exposure to tetrazepam during machine maintenance | journal = Contact Dermatitis | volume = 52 | issue = 3 | pages = 173–4 | date = March 2005 | pmid = 15811045 | doi = 10.1111/j.0105-1873.2005.0548o.x | s2cid = 30499424 }}

File:Epikutanni-test.jpg]]

Patch testing has been used successfully to demonstrate tetrazepam allergy.{{cite journal | vauthors = Barbaud A, Gonçalo M, Bruynzeel D, Bircher A | s2cid = 10780935 | title = Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions | journal = Contact Dermatitis | volume = 45 | issue = 6 | pages = 321–8 | date = December 2001 | pmid = 11846746 | doi = 10.1034/j.1600-0536.2001.450601.x | doi-access = free }}{{cite journal | vauthors = Barbaud A, Trechot P, Reichert-Penetrat S, Granel F, Schmutz JL | title = The usefulness of patch testing on the previously most severely affected site in a cutaneous adverse drug reaction to tetrazepam | journal = Contact Dermatitis | volume = 44 | issue = 4 | pages = 259–60 | date = April 2001 | pmid = 11336014 | doi = 10.1034/j.1600-0536.2001.440409-15.x | s2cid = 40786622 }} Oral testing can also be used. Skin prick tests are not always accurate and may produce false negatives.{{cite journal | vauthors = Sánchez-Morillas L, Laguna-Martínez JJ, Reaño-Martos M, Rojo-Andrés E, Ubeda PG | title = Systemic dermatitis due to tetrazepam | journal = Journal of Investigational Allergology & Clinical Immunology | volume = 18 | issue = 5 | pages = 404–6 | year = 2008 | pmid = 18973107 | url = http://www.jiaci.org/issues/vol18issue5/14.pdf }}

Drowsiness is a common side effect of tetrazepam.{{cite journal | vauthors = Rode G, Maupas E, Luaute J, Courtois-Jacquin S, Boisson D | title = [Medical treatment of spasticity] | journal = Neuro-Chirurgie | volume = 49 | issue = 2–3 Pt 2 | pages = 247–55 | date = May 2003 | pmid = 12746699 }} A reduction in muscle force can occur.{{cite journal | vauthors = Lobisch M, Schaffler K, Wauschkuhn H, Nickel B | title = [Clinical pilot study of the myogenic effects of flupirtine in comparison to tetrazepam and placebo] | journal = Arzneimittel-Forschung | volume = 46 | issue = 3 | pages = 293–8 | date = March 1996 | pmid = 8901152 }} Myasthenia gravis, a condition characterised by severe muscle weakness is another potential adverse effect from tetrazepam.{{cite journal | vauthors = Vargas Ortega I, Canora Lebrato J, Díez Ruiz A, Rico Irles J | title = [Myasthenia gravis after tetrazepam treatment] | journal = Anales de Medicina Interna | volume = 17 | issue = 12 | pages = 669 | date = December 2000 | pmid = 11213590 | doi = 10.4321/s0212-71992000001200016 | doi-access = free }} Cardiovascular and respiratory adverse effects can occur with tetrazepam similar to other benzodiazepines.

{{See also|Benzodiazepine withdrawal syndrome}}

Prolonged use, as with all benzodiazepines, should be avoided, as tolerance occurs and there is a risk of benzodiazepine dependence and a benzodiazepine withdrawal syndrome after stopping or reducing dosage.

{{See also|Benzodiazepine overdose}}

Tetrazepam, like other benzodiazepines is a drug which is very frequently present in cases of overdose. These overdoses are often mixed overdoses, i.e. a mixture of other benzodiazepines or other drug classes with tetrazepam.{{cite journal | vauthors = Zevzikovas A, Bertulyte A, Dirse V, Ivanauskas L | title = [Determination of benzodiazepine derivatives mixture by high performance liquid chromatography] | journal = Medicina | volume = 39 | pages = 30–6 | year = 2003 | issue = Suppl 2 | pmid = 14617855 }}{{cite journal | vauthors = Zevzikovas A, Kiliuviene G, Ivanauskas L, Dirse V | title = [Analysis of benzodiazepine derivative mixture by gas-liquid chromatography] | language = lithuanian | journal = Medicina | volume = 38 | issue = 3 | pages = 316–20 | year = 2002 | pmid = 12474705 | url = http://medicina.kmu.lt/0203/0203-12l.pdf | access-date = 2009-09-14 | archive-date = 2011-07-22 | archive-url = https://web.archive.org/web/20110722151944/http://medicina.kmu.lt/0203/0203-12l.pdf | url-status = dead }}

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.{{cite journal | vauthors = Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, Vennat B, Llorca PM, Eschalier A | title = Benzodiazepine dependence: focus on withdrawal syndrome | journal = Annales Pharmaceutiques Françaises | volume = 67 | issue = 6 | pages = 408–13 | date = November 2009 | pmid = 19900604 | doi = 10.1016/j.pharma.2009.07.001 }}

Tetrazepam is an unusual benzodiazepine in its molecular structure as it has cyclohexenyl group which has substituted the typical 5-phenyl moiety seen in other benzodiazepines.{{cite journal | vauthors = Pavlic M, Libiseller K, Grubwieser P, Schubert H, Rabl W | title = Medicolegal aspects of tetrazepam metabolism | journal = International Journal of Legal Medicine | volume = 121 | issue = 3 | pages = 169–74 | date = May 2007 | pmid = 17021899 | doi = 10.1007/s00414-006-0118-6 | s2cid = 32405914 }}

Tetrazepam, is rapidly absorbed after oral administration, within 45 mins and reaches peak plasma levels in less than 2 hours. It is classed as an intermediate acting benzodiazepine with an elimination half-life of approximately 15 hours. It is primarily metabolised to the inactive metabolites 3-hydroxy-tetrazepam and nortetrazepam.{{cite journal | vauthors = Baumgärtner MG, Cautreels W, Langenbahn H | title = Biotransformation and pharmacokinetics of tetrazepam in man | journal = Arzneimittel-Forschung | volume = 34 | issue = 6 | pages = 724–9 | year = 1984 | pmid = 6148954 }} The pharmacological effects of tetrazepam are significantly less potent when compared against diazepam, in animal studies.{{cite journal | vauthors = Keane PE, Simiand J, Morre M, Biziere K | title = Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. I. Psychopharmacological profile in rodents | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 245 | issue = 2 | pages = 692–8 | date = May 1988 | pmid = 2896794 }} Tetrazepam is a benzodiazepine site agonist and binds unselectively to type 1 and type 2 benzodiazepine site types as well as to peripheral benzodiazepine receptors.{{cite journal | vauthors = Keane PE, Bachy A, Morre M, Biziere K | title = Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. II. In vitro and in vivo interactions with benzodiazepine binding sites | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 245 | issue = 2 | pages = 699–705 | date = May 1988 | pmid = 2896795 }} The muscle relaxant properties of tetrazepam are most likely due to a reduction of calcium influx.{{cite journal | vauthors = Pérez-Guerrero C, Suárez J, Herrera MD, Marhuenda E | title = Spasmolytic effects of tetrazepam on rat duodenum and guinea-pig ileum | journal = Pharmacological Research | volume = 35 | issue = 5 | pages = 493–7 | date = May 1997 | pmid = 9299217 | doi = 10.1006/phrs.1997.0173 }} Small amounts of diazepam as well as the active metabolites of diazepam are produced from metabolism of tetrazepam.{{cite journal | vauthors = Baumann A, Lohmann W, Schubert B, Oberacher H, Karst U | title = Metabolic studies of tetrazepam based on electrochemical simulation in comparison to in vivo and in vitro methods | journal = Journal of Chromatography A | volume = 1216 | issue = 15 | pages = 3192–8 | date = April 2009 | pmid = 19233363 | doi = 10.1016/j.chroma.2009.02.001 }}{{cite journal | vauthors = Schubert B, Pavlic M, Libiseller K, Oberacher H | title = Unraveling the metabolic transformation of tetrazepam to diazepam with mass spectrometric methods | journal = Analytical and Bioanalytical Chemistry | volume = 392 | issue = 7–8 | pages = 1299–308 | date = December 2008 | pmid = 18949465 | doi = 10.1007/s00216-008-2447-4 | s2cid = 10967477 }} The metabolism of tetrazepam has led to false accusations of prisoners prescribed tetrazepam of taking illicit diazepam; this can lead to increased prison sentences for prisoners.

{{See also|Drug-related crime|Benzodiazepine misuse}}

Tetrazepam as with other benzodiazepines is sometimes abused. It is sometimes abused to incapacitate a victim in order to carry out a drug-facilitated crime.{{cite journal | vauthors = Concheiro M, Villain M, Bouchet S, Ludes B, López-Rivadulla M, Kintz P | title = Windows of detection of tetrazepam in urine, oral fluid, beard, and hair, with a special focus on drug-facilitated crimes | journal = Therapeutic Drug Monitoring | volume = 27 | issue = 5 | pages = 565–70 | date = October 2005 | pmid = 16175127 | doi = 10.1097/01.ftd.0000164610.14808.45 | s2cid = 45605607 }} or abused in order to achieve a state of intoxication.{{cite journal | vauthors = Kintz P, Villain M, Concheiro M, Cirimele V | title = Screening and confirmatory method for benzodiazepines and hypnotics in oral fluid by LC-MS/MS | journal = Forensic Science International | volume = 150 | issue = 2–3 | pages = 213–20 | date = June 2005 | pmid = 15944062 | doi = 10.1016/j.forsciint.2004.12.040 }}

Tetrazepam's abuse for to carry out drug facilitated crimes may be less however, than other benzodiazepines due to its reduced hypnotic properties.{{cite journal | vauthors = Laloup M, Fernandez M, Wood M, Maes V, De Boeck G, Vanbeckevoort Y, Samyn N | title = Detection of diazepam in urine, hair and preserved oral fluid samples with LC-MS-MS after single and repeated administration of Myolastan and Valium | journal = Analytical and Bioanalytical Chemistry | volume = 388 | issue = 7 | pages = 1545–56 | date = August 2007 | pmid = 17468852 | doi = 10.1007/s00216-007-1297-9 | s2cid = 19256926 }}

• Benzodiazepine
• Long-term effects of benzodiazepines

{{Reflist|32em}}

{{Benzodiazepines}}

{{Muscle relaxants}}

{{GABAAR PAMs}}

Category:Benzodiazepines

Category:Chloroarenes

Category:Lactams

Category:Cyclohexenes