Editing Benzodiazepine (section)

==Chemistry==
[[File:Benzodiazepine3.png|thumb|class=skin-invert-image|alt=On the left is the chemical structure of the parent benzodiazepine ring system, which consists of a seven-membered ring containing two nitrogen atoms fused to a six-membered ring. The two nitrogen atoms are labeled one and four. On the right is the chemical structure of a pharmacologically active benzodiazepine in which alkyl, phenyl, and halogen groups attach to the one, five, and seven positions, respectively, and the carbon atom at position two is double-bonded to an exocyclic oxygen atom. The ortho and para positions of the phenyl substituent are labeled two-prime and 4-prime, respectively.|'''Left''': The 1,4-benzodiazepine ring system. '''Right''': 5-phenyl-1''H''-benzo[''e''] [1,4]diazepin-2(3''H'')-one forms the skeleton of many of the most common benzodiazepine pharmaceuticals, such as [[diazepam]] (7-chloro-1-methyl substituted).]]
[[File:Bzr pm.png|thumb|class=skin-invert-image|alt=Superposition of the chemical structures of a benzodiazepine and nonbenzodiazepine ligand and their interactions with binding sites within the receptor.|A [[pharmacophore]] model of the benzodiazepine binding site on the GABA<sub>A</sub> receptor.<ref name="isbn0-471-21384-5"/> White sticks represent the carbon atoms of the benzodiazepine [[diazepam]], while green represents carbon atoms of the nonbenzodiazepine [[CGS-9896]]. Red and blue sticks are oxygen and nitrogen atoms that are present in both structures. The red spheres labeled H1 and H2/A3 are, respectively, [[hydrogen bond]] donating and accepting sites in the receptor, while L1, L2, and L3 denote [[lipophilicity|lipophilic]] binding sites.]]
Benzodiazepines share a similar chemical structure, and their effects in humans are mainly produced by the [[allosteric]] modification of a specific kind of [[neurotransmitter receptor]], the [[GABAA receptor|GABA<sub>A</sub> receptor]], which increases the overall conductance of these inhibitory channels; this results in the various therapeutic effects as well as adverse effects of benzodiazepines.<ref name="isbn0-12-088397-X"/> Other less important [[mode of action|modes of action]] are also known.<ref name="pmid9504140"/><ref name="pmid16780077"/>

The term ''benzodiazepine'' is the [[IUPAC nomenclature|chemical name]] for the [[heterocycle|heterocyclic]] ring system (see figure to the right), which is a fusion between the [[benzene]] and [[diazepine]] ring systems.<ref name=IUPAC>{{BlueBook1993 |pages=40–43 }}; {{cite journal |publisher=Moss GP |year=1998 |title=Nomenclature of fused and bridged fused ring systems (IUPAC Recommendations 1998) |url=http://media.iupac.org/publications/pac/1998/pdf/7001x0143.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://media.iupac.org/publications/pac/1998/pdf/7001x0143.pdf |archive-date=9 October 2022 |url-status=live |journal=Pure and Applied Chemistry |volume=70 |issue=1 |pages=143–216 |doi=10.1351/pac199870010143 |s2cid=5776706 | vauthors = Moss GP }}</ref> Under [[Hantzsch–Widman nomenclature]], a [[diazepine]] is a heterocycle with two [[nitrogen]] atoms, five [[carbon]] atom and the maximum possible number of cumulative [[double bond]]s. The "benzo" prefix indicates the [[benzene]] ring fused onto the diazepine ring.<ref name="IUPAC" />

Benzodiazepine drugs are substituted 1,4-benzodiazepines, although the chemical term can refer to many other compounds that do not have useful pharmacological properties. Different benzodiazepine drugs have different side groups attached to this central structure. The different side groups affect the binding of the molecule to the GABA<sub>A</sub> receptor and so modulate the pharmacological properties.<ref name="isbn0-12-088397-X"/> Many of the pharmacologically active "classical" benzodiazepine drugs contain the 5-phenyl-1''H''-benzo[''e''] [1,4]diazepin-2(3''H'')-one substructure (see figure to the right).<ref name=CAS>[[CAS registry number]]:{{CAS|2898-08-0|1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one}}; other names: Ro 05-2921, dechlorodemethyldiazepam.</ref> Benzodiazepines have been found to mimic protein reverse turns structurally, which enable them with their biological activity in many cases.<ref>{{cite journal |vauthors=Ripka WC, De Lucca GV, Bach AC, Pottorf RS, Blaney JM | title = Protein β-turn mimetics I. Design, synthesis, and evaluation in model cyclic peptides | journal = Tetrahedron | volume = 49 | issue = 17 | pages = 3593–3608 | year = 1993 | doi = 10.1016/S0040-4020(01)90217-0 }}</ref><ref>{{cite journal |vauthors=Hata M, Marshall GR | title = Do benzodiazepines mimic reverse-turn structures? | journal = Journal of Computer-Aided Molecular Design | volume = 20 | issue = 5 | pages = 321–331 | year = 2006 | pmid = 16972167 | doi = 10.1007/s10822-006-9059-x | bibcode = 2006JCAMD..20..321H | s2cid = 2777635 }}</ref>

[[Nonbenzodiazepine]]s also bind to the benzodiazepine binding site on the GABA<sub>A</sub> receptor and possess similar pharmacological properties. While the nonbenzodiazepines are by definition structurally unrelated to the benzodiazepines, both classes of drugs possess a common [[pharmacophore]] (see figure to the lower-right), which explains their binding to a common receptor site.<ref name="isbn0-471-21384-5">{{cite book |vauthors=Madsen U, Bräuner-Osborne H, Greenwood JR, Johansen TN, Krogsgaard-Larsen P, Liljefors T, Nielsen M, Frølund B |editor=Gad SC |title=Drug Discovery Handbook |publisher=Wiley-Interscience/J. Wiley |location=Hoboken, N.J |year=2005 |pages=797–907 |chapter=GABA and Glutamate receptor ligands and their therapeutic potential in CNS disorders |isbn=978-0-471-21384-0 }}</ref>

Not all benzodiazepines increase the conductance of the GABA<sub>A</sub> receptor. [[Flumazenil]], an imidazobenzodiazepine, is an antidote for some benzodiazepine overdoses.<ref>{{cite journal | vauthors = Hood SD, Norman A, Hince DA, Melichar JK, Hulse GK | title = Benzodiazepine dependence and its treatment with low dose flumazenil | journal = British Journal of Clinical Pharmacology | volume = 77 | issue = 2 | pages = 285–294 | date = February 2014 | pmid = 23126253 | pmc = 4014019 | doi = 10.1111/bcp.12023 }}</ref> The structual scaffold can even be used to target receptors other than GABA<sub>A</sub>.<ref>{{cite journal | vauthors = Mian MY, Sharmin D, Mondal P, Belayet JB, Hossain MM, McCusker P, Ryan KT, Fedorov AY, Green HA, Ericksen SS, Zamanian M, Tiruveedhula VV, Cook JM, Chan JD | title = Development of non-sedating benzodiazepines with ''in vivo'' antischistosomal activity | journal = Antimicrobial Agents and Chemotherapy | volume = 68 | issue = 9 | pages = e0036924 | date = September 2024 | pmid = 39136467 | doi = 10.1128/aac.00369-24 | pmc = 11373208 }}</ref>

===Types===
* 2-keto compounds:
::[[clorazepate]], [[diazepam]], [[flurazepam]], [[halazepam]], [[prazepam]], and others<ref name=ub>{{cite web| vauthors = Juergens SM |title=Understanding Benzodiazepines|url=http://www.csam-asam.org/sites/default/files/pdf/misc/Juergens.pdf|publisher=California Society of Addiction Medicine|access-date=25 April 2012|archive-url=https://web.archive.org/web/20120508050910/http://www.csam-asam.org/sites/default/files/pdf/misc/Juergens.pdf|archive-date=8 May 2012|url-status=dead}}</ref><ref name=PC89>{{cite journal |vauthors=Carlo P, Finollo R, Ledda A, Brambilla G | title = Absence of liver DNA fragmentation in rats treated with high oral doses of 32 benzodiazepine drugs | journal = Fundamental and Applied Toxicology | volume = 12 | issue = 1 | pages = 34–41 | date = January 1989 | pmid = 2925017 | doi = 10.1016/0272-0590(89)90059-6 }}</ref>
* 3-hydroxy compounds:
::[[lorazepam]], [[lormetazepam]], [[oxazepam]], [[temazepam]]<ref name=ub/><ref name=PC89/>
* 7-nitro compounds:
::[[clonazepam]], [[flunitrazepam]], [[nimetazepam]], [[nitrazepam]]<ref name=ub/><ref name=PC89/>
* Triazolo compounds:
::[[adinazolam]], [[alprazolam]], [[estazolam]], [[triazolam]]<ref name=ub/><ref name=PC89/>
* Imidazo compounds:
::[[climazolam]], [[loprazolam]], [[midazolam]]<ref name=ub/><ref name=PC89/>
* 1,5-benzodiazepines:
::[[clobazam]]