Pentylenetetrazol: Difference between revisions

{{drugbox | verifiedrevid = 386830665

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| IUPAC_name = 6,7,8,9-Tetrahydro-5''H''-tetrazolo(1,5-''a'')azepine

| image = Pentylenetetrazol.svg

| CASNo_Ref = {{cascite}}

| CAS_number = 54-95-5

| ATC_prefix = R07

| ATC_suffix = AB03

| PubChem = 5917

| DrugBank =

| smiles = C12=NN=N[N]1CCCCC2

| C=6 | H=10 | N=4

| molecular_weight = 138.171

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| 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 =

'''Pentylenetetrazol''' ([[International Nonproprietary Name|INN]]), also known as metrazol, pentetrazol, pentamethylenetetrazol, Cardiazol or PTZ, is a drug used as a circulatory and respiratory stimulant. High doses cause [[convulsions]], as discovered by the Hungarian-American neurologist and psychiatrist [[Ladislas J. Meduna]] in 1934. It has been used in convulsive therapy, but was never considered to be effective, and side-effects such as [[seizure]]s were difficult to avoid. Its approval by the [[Food and Drug Administration|FDA]] was revoked in 1982.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 is considered a [[GABA antagonist]].<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=mesh&list_uids=68010433&dopt=Full Entry for Pentylenetetrazole] in the [[Medical Subject Headings|MeSH]] database</ref> The [[mechanism of action|mechanism]] of the [[epileptogenic]] action of pentylenetetrazol at the cellular [[neurons|neuronal]] level is still unclear. [[Electrophysiology|Electrophysiological]] studies have shown it acts at [[cell membrane]] level decreasing the recovery time between [[action potential]]s by increasing [[potassium]] [[Semipermeable membrane|permeability]] of the [[axon]]. Other studies have implicated an increase in membrane currents of several other ions, such as [[sodium]] and [[calcium]], leading to an overall increase in [[excitability]] of the neuron membrane.

==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 [[anxiety]]. Pentylenetetrazol produces a reliable [[discriminative stimulus]] which is largely mediated by the [[GABA A receptor|GABA_A]] receptor. Several classes of compounds can modulate the pentylenetetrazol discriminative stimulus including [[5-HT1A|5-HT_1A]], [[5-HT3|5-HT₃]], [[NMDA]], [[glycine]], and [[L-type calcium channel]] [[ligands]].<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>

Recently, Stanford University researchers have renewed interest in PTZ as a candidate for pharmacological treatment of [[Down syndrome]]. Published in the April 2007 issue of [[Nature Neuroscience]], their brief communication outlined an experiment designed to test the underlying theory proposed to explain the purported efficacy of [[GABA A receptor|GABA_A]] antagonists in restoring the [[declarative memory]] deficits associated with the mouse model of human Down Syndrome. Ts65Dn mice injected with a 2-week regiment of either of two compounds [[picrotoxin]] or [[bilobalide]] (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 [[Long-term potentiation]] in the [[dentate gyrus]] 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>

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 [[circadian rhythm]] (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==

In 1939, pentylenetetrazol was replaced by [[electroconvulsive therapy]] as the preferred method for inducing seizures in England's mental hospitals.

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{{GABAergics}}

[[Category:GABA antagonists]]

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