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| 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> | 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> | ||
| 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> | 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> | ||
| The finding of pentylenetetrazol's effectiveness in treating Down |
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== | ==Alternatives== | ||
Revision as of 21:50, 25 February 2011
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| ECHA InfoCard | 100.000.200  |
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| Formula | C6H10N4 |
| Molar mass | 138.171 g·mol |
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Pentylenetetrazol (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 seizures were difficult to avoid. Its approval by the FDA was revoked in 1982.
Mechanism
Pentylenetetrazol is considered a GABA antagonist. The mechanism of the epileptogenic action of pentylenetetrazol at the cellular neuronal level is still unclear. Electrophysiological studies have shown it acts at cell membrane level decreasing the recovery time between action potentials by increasing potassium 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 GABAA receptor. Several classes of compounds can modulate the pentylenetetrazol discriminative stimulus including 5-HT1A, 5-HT3, NMDA, glycine, and L-type calcium channel ligands.
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 GABAA 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.
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.
Alternatives
In 1939, pentylenetetrazol was replaced by electroconvulsive therapy as the preferred method for inducing seizures in England's mental hospitals.
References
- JR Minkel (February 25, 2007). "Drug May Counteract Down Syndrome". Scientific American. Retrieved 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. doi:10.1016/S0149-7634(02)00010-6. PMID 12204190.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - 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" (PDF). Nat Neurosci. 10 (4): 411–413. doi:10.1038/nn1860. PMID 17322876.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - 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
| Other respiratory system products (R07) | |
|---|---|
| Lung surfactants | |
| Respiratory stimulants | |
| 5-HT4 receptor agonists | |
| Other agents for treating respiratory depression | |