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			{{Short description|Chemical compound}}
	{{drugbox | verifiedrevid = 386830665
			{{cs1 config|name-list-style=vanc|display-authors=6}}
	|
			{{Drugbox
	| IUPAC_name = 6,7,8,9-Tetrahydro-5''H''-tetrazolo(1,5-''a'')azepine
			| Verifiedfields = changed
	| image = Pentylenetetrazol.svg
			| Watchedfields = changed
	| CASNo_Ref = {{cascite}}
			| verifiedrevid = 415933541
	| CAS_number = 54-95-5
			| IUPAC_name = 6,7,8,9-Tetrahydro-5''H''-tetrazolo(1,5-''a'')azepine
	| ATC_prefix = R07
			| image = Pentylenetetrazol.svg
	| ATC_suffix = AB03
			| width = 150
	| PubChem = 5917
			| image2 = File:Pentylenetetrazol ball-and-stick model.png
	| DrugBank =
			<!--Clinical data-->
	| smiles = C12=NN=N1CCCCC2
			| tradename = Metrazol, others
	| C=6 | H=10 | N=4
			| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
	| molecular_weight = 138.171
			| pregnancy_US = <!-- A / B / C / D / X -->
	| bioavailability =
			| pregnancy_category =
	| protein_bound =
			| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
	| metabolism =
			| legal_UK = <!-- GSL / P / POM / CD -->
	| elimination_half-life =
			| legal_US = <!-- OTC / Rx-only -->
	| excretion =
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		| legal_status =
	| pregnancy_US = <!-- A / B / C / D / X -->
	| pregnancy_category =
	| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
	| legal_UK = <!-- GSL / P / POM / CD -->
	| legal_US = <!-- OTC / Rx-only -->
	| legal_status =
	| routes_of_administration =		| routes_of_administration =
			<!--Pharmacokinetic data-->
			| bioavailability =
			| protein_bound =
			| metabolism =
			| elimination_half-life =
			| excretion =
			<!--Identifiers-->
			| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 54-95-5
			| ATC_prefix = R07
			| ATC_suffix = AB03
			| PubChem = 5917
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank =
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| ChemSpiderID = 5704
			| UNII_Ref = {{fdacite|changed|FDA}}
			| UNII = WM5Z385K7T
			| ChEBI_Ref = {{ebicite|changed|EBI}}
			| ChEBI = 34910
			| ChEMBL_Ref = {{ebicite|changed|EBI}}
			| ChEMBL = 116943
			| KEGG_Ref = {{keggcite|changed|kegg}}
			| KEGG = D07409
			| synonyms = PTZ; Pentylenetetrazole; Leptazol; Metrazol; Pentetrazol; Pentamethylenetetrazol
			<!--Chemical data-->
			| C = 6 | H = 10 | N = 4
			| smiles = C1CCc2nnnn2CC1
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChI = 1S/C6H10N4/c1-2-4-6-7-8-9-10(6)5-3-1/h1-5H2
			| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChIKey = CWRVKFFCRWGWCS-UHFFFAOYSA-N
	}}		}}
	'''Pentylenetetrazol''' (]), also known as metrazol, pentetrazol, pentamethylenetetrazol, Cardiazol or PTZ, is a drug used as a circulatory and respiratory stimulant. High doses cause ], as discovered by the Hungarian-American neurologist and psychiatrist ] in 1934. It has been used in convulsive therapy, but was never considered to be effective, and side-effects such as ]s were difficult to avoid. Its approval by the ] was revoked in 1982.<ref name="sciam">{{cite news | author = JR Minkel | title = Drug May Counteract Down Syndrome | url = http://www.sciam.com/article.cfm?chanID=sa003&articleID=F9E196DB-E7F2-99DF-385C9F38537F58D6 | publisher = Scientific American | date = February 25, 2007 | accessdate = 2007-03-20}}</ref>		'''Pentylenetetrazol''' ('''PTZ'''), also known as '''pentylenetetrazole''', '''leptazol''', '''metrazol''', '''pentetrazol''' (]), '''pentamethylenetetrazol''', '''Corazol''', '''Cardiazol''', or '''Deumacard''', is a drug formerly used as a circulatory and respiratory stimulant. High doses cause ], as discovered by Hungarian-American neurologist and psychiatrist ] in 1934. It has been used in convulsive therapy, and was found to be effective—primarily for depression—but side effects such as uncontrolled ]s were difficult to avoid.<ref>{{cite journal | vauthors = Read CF |title=Consequences of metrazol shock therapy |journal=American Journal of Psychiatry |volume=97 |issue=3 |year=1940 |pages=667–76 |doi=10.1176/ajp.97.3.667 }}</ref> In 1939, pentylenetetrazol was replaced by ], which is easier to administer, as the preferred method for inducing seizures in England's mental hospitals. In the US, its approval by the ] was revoked in 1982.<ref name="sciam">{{ cite news | author = Minkel JR | title = Drug May Counteract Down Syndrome | url = http://www.scientificamerican.com/article/drug-may-counteract-down/ | newspaper = Scientific American | date = February 25, 2007 | access-date = 2007-03-20}}</ref> It is used in Italy as a cardio-respiratory stimulant in combination with ] in a ] drug.<ref>{{cite web|url=https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_007046_021473_FI.pdf&retry=0&sys=m0b1l3|title=Cardiazol-Paracodina |publisher=Agenzia Italiana del Farmaco}}</ref>
			==Side effects==
			Pentylenetetrazol is ] and has been known to induce severe ] in humans.<ref name="DurantChristmasNutt2009">{{cite book | vauthors = Durant C, Christmas D, Nutt D | title=Current Topics in Behavioral Neurosciences | chapter=The Pharmacology of Anxiety | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | year=2009 | isbn=978-3-642-02911-0 | issn=1866-3370 | doi=10.1007/7854_2009_8 | page=303–330 | quote=Preliminary evidence that reducing GABAergic transmission induces anxiety came from the early use of pentylenetetrazol (PTZ) a convulsant drug used to induce seizures in the treatment of severe psychiatric disorders before the discovery of ECT. During its use dose titration was difficult, in many cases too little was given and no seizure was caused. This, however, produced a severely anxious state, leading to patients feeling ‘as if they were going to die’, and trying (often successfully) to escape from the clinic. Memory of this anxiety was extremely strong resulting in resistance to return to therapy and it was later shown that PTZ acts as an antagonist GABAA receptor.}}</ref>
	==Mechanism==		==Mechanism==
			The mechanism of pentylenetetrazol is not well understood, and it may have multiple ]. In 1984, Squires et al. published a report analyzing pentylenetetrazol and several structurally related convulsant drugs. They found that ''in vivo'' convulsant potency was strongly correlated to ''in vitro'' affinity to the ] binding site on the ] complex. Many GABA-A ligands, such as the ]s ] and ], are effective ], but presumably pentylenetetrazol has the opposite effect when it binds to the GABA-A receptor.<ref>{{cite journal | vauthors = Squires RF, Saederup E, Crawley JN, Skolnick P, Paul SM | title = Convulsant potencies of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain | journal = Life Sciences | volume = 35 | issue = 14 | pages = 1439–1444 | date = October 1984 | pmid = 6090836 | doi = 10.1016/0024-3205(84)90159-0 }}</ref>
	Pentylenetetrazol is considered a ].<ref> in the ] database</ref> The ] of the ] action of pentylenetetrazol at the cellular ] level is still unclear. ] studies have shown it acts at ] level decreasing the recovery time between ]s by increasing ] ] of the ]. Other studies have implicated an increase in membrane currents of several other ions, such as ] and ], leading to an overall increase in ] of the neuron membrane.
			Several studies have focused on the way pentylenetetrazol influences neuronal ion channels. A 1987 study found that pentylenetetrazol increases calcium influx and sodium influx, both of which depolarize the neuron. Because these effects were antagonized by calcium channel blockers, pentylenetetrazol apparently acts at calcium channels, and it causes them to lose selectivity and conduct sodium ions, as well.<ref>{{cite journal | vauthors = Papp A, Fehér O, Erdélyi L | title = The ionic mechanism of the pentylenetetrazol convulsions | journal = Acta Biologica Hungarica | volume = 38 | issue = 3–4 | pages = 349–361 | year = 1987 | pmid = 3503442 }}</ref>
	==Uses==
	Pentylenetetrazol has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. Pentylenetetrazol is also a prototypical anxiogenic drug and, has been extensively utilized in animal models of ]. Pentylenetetrazol produces a reliable ] which is largely mediated by the ] receptor. Several classes of compounds can modulate the pentylenetetrazol discriminative stimulus including ], ], ], ], and ] ].<ref>{{cite journal |author=Jung M, Lal H, Gatch M |title=The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: recent developments |journal=Neurosci Biobehav Rev |volume=26 |issue=4 |pages=429–39 |year=2002 |pmid=12204190 |doi=10.1016/S0149-7634(02)00010-6}}</ref>
			==Research==
	Recently, Stanford University researchers have renewed interest in PTZ as a candidate for pharmacological treatment of ]. Published in the April 2007 issue of ], their brief communication outlined an experiment designed to test the underlying theory proposed to explain the purported efficacy of ] antagonists in restoring the ] deficits associated with the mouse model of human Down Syndrome. Ts65Dn mice injected with a 2-week regiment of either of two compounds ] or ] (both GABA antagonists) showed marked improvements in both exploration and recognition of novel objects over controls injected with only saline. These results were duplicated in a second experiment with mice fed either plain milk or a combination of milk and a non-epileptogenic dose of PTZ daily for 17 days. PTZ-fed mice achieved novel object task scores comparable to wild-type (normal) mice. These improvements persisted at least 1 to 2 months after the treatment regiment. Not surprisingly these compounds' efficacies were accompanied by the normalization of ] in the ] one month after the end of treatment, further suggesting persistent drug-mediated improvements in learning and memory.<ref>{{cite journal |author=Fernandez F, Morishita W, Zuniga E, Nguyen J, Blank M, Malenka R, Garner C |title=Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome |journal=Nat Neurosci |volume=10 |issue=4 |pages=411–413 |year=2007 |url=http://med.stanford.edu/nbc/articles/7%20-%20Pharmacotherapy%20for%20Cognitive%20Impairment%20in%20a%20Mouse%20Model%20of%20Down%20Syndrome.pdf |pmid=17322876 |doi=10.1038/nn1860}}</ref>
			Pentylenetetrazol has been used experimentally to study seizure phenomena and to identify pharmaceuticals that may control seizure susceptibility. For instance, researchers can induce ] in animal models. Pentylenetetrazol is also a prototypical ] drug and has been extensively used in animal models of ]. Pentylenetetrazol produces a reliable ], which is largely mediated by the ] receptor. Several classes of compounds can modulate the pentylenetetrazol discriminative stimulus, including ], ], ], ], and ] ].<ref>{{cite journal | vauthors = Jung ME, Lal H, Gatch MB | title = The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: recent developments | journal = Neuroscience and Biobehavioral Reviews | volume = 26 | issue = 4 | pages = 429–439 | date = June 2002 | pmid = 12204190 | doi = 10.1016/S0149-7634(02)00010-6 | s2cid = 26055062 }}</ref>
			Pentylenetetrazol is being studied as a ] in the treatment of idiopathic ] and ].<ref name="AdisInsight">{{cite web | title=Pentylenetetrazole - Balance Therapeutics | work = AdisInsight | publisher = Springer Nature Switzerland AG | date=28 June 2020 | url=https://adisinsight.springer.com/drugs/800038901 | access-date=25 September 2024}}</ref><ref name="TakahashiNoriakiMatsumura2018">{{cite journal | vauthors = Takahashi T, Noriaki S, Matsumura M, Li C, Takahashi K, Nishino S | title=Advances in pharmaceutical treatment options for narcolepsy | journal=Expert Opinion on Orphan Drugs | volume=6 | issue=10 | date=3 October 2018 | issn=2167-8707 | doi=10.1080/21678707.2018.1521267 | pages=597–610}}</ref>
	The finding of pentylenetetrazol's effectiveness in treating a mouse model of Down syndrome has led to it being explored as a means of correcting other learning deficiencies. Specifically, hamsters denied their natural ] (though not denied sleep) had their memory restored to near-normal levels when treated with pentylenetetrazol.<ref>Ruby et al.; Hippocampal-dependent learning requires a functional circadian system; Proceedings of the National Academy of Sciences of the United States of America, 2008, vol. 105, no. 40,15593-15598</ref>
	==Alternatives==		== See also ==
			* ]
	In 1939, pentylenetetrazol was replaced by ] as the preferred method for inducing seizures in England's mental hospitals.
			* ]
			* ]
	==References==		== References ==
	{{reflist|2}}		{{Reflist|30em}}
	{{Respiratory stimulants}}		{{Respiratory stimulants}}
	{{GABAergics}}		{{Convulsants}}
			{{GABA receptor modulators}}
			]<!--Convulsive therapy-->
			]
			]
			]
			]
	]		]
	]		]
			]
	]		]
	]
	]
	]
	]
	]