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Pentylenetetrazol chemical structure
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Pentylenetetrazol (PTZ) is the International Nonproprietary Name of Metrazol (aka Cardiazol in Europe) and also known as pentetrazol or pentamethylenetetrazol. It is a drug used as a circulatory and respiratory stimulant. Larger doses cause convulsions, thus it was commonly used in shock therapy during the 40s and 50s, as first used by the Hungarian-American neurologist and psychiatrist Ladislas J. Meduna in 1934.
Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. PTZ is also a prototypical anxiogenic drug and, has been extensively utilized in animal models of anxiety. PTZ produces a reliable discriminative stimulus which is largely mediated by the GABAA receptor. Several classes of compounds can modulate the PTZ discriminative stimulus including 5-HT1A, 5-HT3, NMDA, glycine, and L-type calcium channel ligands.
Recently, it has been shown that pentetrazol at non-epileptic doses, along with two other compounds (Picrotoxin and bilobalide) can restore the cognitive function (learning and memory) of a mouse model of Down syndrome by inhibiting GABAA receptor without inducing seizures. These results caused renewed interest in pentetrazol as a potential drug candidate for Down syndrome, although clinical trials are probably still a couple of years away..
The finding of pentetrazol's effectiveness in treating Down Syndrome has lead 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 pentetrazol.
In 1939, Metrazol (also known as Cardiazol) was replaced by electroconvulsive therapy as the preferred method for inducing seizures in England's mental hospitals.
- ↑ 1.0 1.1 includeonly>JR Minkel. "Drug May Counteract Down Syndrome", Scientific American, February 25, 2007. Retrieved on 2007-03-20.
- ↑ Entry for Pentylenetetrazole in the MeSH database
- ↑ Jung M, Lal H, Gatch M (2002). The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: recent developments. Neurosci Biobehav Rev 26 (4): 429–39.
- ↑ Fernandez F, Morishita W, Zuniga E, Nguyen J, Blank M, Malenka R, Garner C (2007). Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat Neurosci.
- ↑ 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
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