Thienodiazepines: Difference between revisions

{{Headerpanel|{{DepressantOD|thienodiazepines}}{{stub}}}}

[[File:Substituted_thienodiazepine.svg|270px|thumbnail|right|The general structure of Thienodiazepines.]]

A '''thienodiazepine''' is a heterocyclic compound containing a diazepine ring fused to a thiophene ring. The thienodiazepine ring structure forms the central core of several pharmaceutical drugs. Since thienodiazepines interact with the [[benzodiazepine]] receptor site, they typically have similar effects as benzodiazepines and can be considered as essentially identical.

 

*'''[[Effect::Dizziness]]'''

*'''[[Effect::Motor control loss]]''' - Lack of coordination may result in falls and injuries, in particular, in the elderly.  Another result of motor control loss is the impairment of driving skills and the increased likelihood of road traffic accidents.

*'''[[Effect::Muscle relaxation]]'''

*'''[[Effect::Physical euphoria]]'''

*'''[[Effect::Sedation]]'''

*'''[[Effect::Seizure suppression]]'''

Paradoxical reactions to thienodiazepines, as well as [[benzodiazepines]], such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).<ref>{{cite journal | vauthors=((Saïas, T.)), ((Gallarda, T.)) | journal=L’Encephale | title=[Paradoxical aggressive reactions to benzodiazepine use: a review] | volume=34 | issue=4 | pages=330–336 | date= September 2008 | issn=0013-7006 | doi=10.1016/j.encep.2007.05.005}}</ref><ref>{{cite journal | vauthors=((Paton, C.)) | journal=Psychiatric Bulletin | title=Benzodiazepines and disinhibition: a review | volume=26 | issue=12 | pages=460–462 | date= December 2002 | url=https://www.cambridge.org/core/journals/psychiatric-bulletin/article/benzodiazepines-and-disinhibition-a-review/421AF197362B55EDF004700452BF3BC6 | issn=0955-6036 | doi=10.1192/pb.26.12.460}}</ref><p>

These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.<ref>{{cite journal | vauthors=((Bond, A. J.)) | journal=CNS Drugs | title=Drug- Induced Behavioural Disinhibition | volume=9 | issue=1 | pages=41–57 | date=1 January 1998 | url=https://doi.org/10.2165/00023210-199809010-00005 | issn=1179-1934 | doi=10.2165/00023210-199809010-00005}}</ref><ref>{{cite journal | vauthors=((Drummer, O. H.)) | journal=Forensic Science Review | title=Benzodiazepines - Effects on Human Performance and Behavior | volume=14 | issue=1–2 | pages=1–14 | date= February 2002 | issn=1042-7201}}</ref></p>

*'''[[Effect::Delusions|Delusions of sobriety]]''' - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages.

*'''[[Effect::Analysis suppression]]'''

 

==List of substituted thienodiazepines==

{| class="wikitable"

! scope="col" | '''Compound'''

! scope="col" style="width: 50px;" | '''R₁'''

! scope="col" style="width: 50px;" | '''R₂'''

! scope="col" style="width: 50px;" | '''R₅'''

! scope="col" style="width: 50px;" | '''R₇'''

! scope="col" style="width: 50px;" | '''R_2''''

! scope="col" | '''Structure'''

| [[Deschloroetizolam]] || C(CH₃)=N- || =N-|| C₆H₅ || CH₂CH₃ || H || [[File:Deschloroetizolam.svg|170px]]

| [[Brotizolam]] || C(CH₃)=N- || =N-|| C₆H₄Cl || Br || Cl || [[File:Brotizolam.svg|170px]]

| [[Fluclotizolam]] || C(CH₃)=N- || =N-|| C₆H₄F || Cl || F || [[File:Fluclotizolam.svg|170px]]

==Preparation methods==

*'''[[Volumetric liquid dosing]]''' - If one's thienodiazepines are in powder form, they are unlikely to weigh out accurately without the most expensive of scales due to their extreme potency. To avoid this, one can dissolve the thienodiazepine volumetrically into a solution so as to dose it accurately based upon the instructions described in [[Volumetric liquid dosing|this tutorial]].

[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.<ref>{{cite journal | vauthors=((Nutt, D.)), ((King, L. A.)), ((Saulsbury, W.)), ((Blakemore, C.)) | journal=The Lancet | title=Development of a rational scale to assess the harm of drugs of potential misuse | volume=369 | issue=9566 | pages=1047–1053 | date=24 March 2007 | url=https://www.sciencedirect.com/science/article/pii/S0140673607604644 | issn=0140-6736 | doi=10.1016/S0140-6736(07)60464-4}}</ref>]]

The median lethal dosage varies widely between specific substances within the thienzodiazepine class. For this reason, one should always fully research the substance before administering it to themselves or others.

It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using these substances.

Tolerance will develop to the sedative-hypnotic effects within a couple of days.<ref>{{cite book | vauthors=((Janicak, P. G.)), ((Marder, S. R.)), ((Pavuluri, M. N.)) | date=25 October 2010 | title=Principles and Practice of Psychopharmacotherapy | publisher=Lippincott Williams & Wilkins | isbn=9781605475653}}</ref> Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.<ref>{{cite journal | vauthors=((Verster, J. C.)), ((Volkerts, E. R.)) | journal=CNS Drug Reviews | title=Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature | volume=10 | issue=1 | pages=45–76 | date=7 June 2006 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2004.tb00003.x | issn=1080563X | doi=10.1111/j.1527-3458.2004.tb00003.x}}</ref> <ref>{{cite book | vauthors=((Galanter, M.)), ((Kleber, H. D.)) | date= 2008 | title=The American Psychiatric Publishing Textbook of Substance Abuse Treatment | publisher=American Psychiatric Pub. | isbn=9781585622764}}</ref>

Similar to benzodiazepines, thienodiazepine discontinuation is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of [[high blood pressure]], [[seizures]], and death.<ref>{{cite journal | vauthors=((Lann, M. A.)), ((Molina, D. K.)) | journal=The American Journal of Forensic Medicine and Pathology | title=A fatal case of benzodiazepine withdrawal | volume=30 | issue=2 | pages=177–179 | date= June 2009 | issn=1533-404X | doi=10.1097/PAF.0b013e3181875aa0}}</ref> Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal. Abrupt discontinuation also causes rebound stimulation which presents as [[anxiety]], [[wakefulness|insomnia]] and restlessness.

The duration and severity of withdrawal symptoms depend on a number of factors including the half-life of the drug used, tolerance and the duration of abuse. Major symptoms will usually start within just a few days after discontinuation and persist for around a week for shorter lasting thienodiazepines. Thienodiazepines with longer half-lives will exhibit withdrawal symptoms with a slow onset and extended duration.