WordNet

a drug used as a circulatory and respiratory stimulant; larger doses cause convulsions in shock therapy; Metrazol is a trademark (同)pentamethylenetetrazol, Metrazol

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/02 22:49:34」(JST)

wiki en

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 Its approval by the FDA was revoked in 1982.^[1]

Mechanism

Pentylenetetrazol is considered a GABA antagonist.^[2] 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 GABA_A receptor. Several classes of compounds can modulate the pentylenetetrazol discriminative stimulus including 5-HT_1A, 5-HT₃, NMDA, glycine, and L-type calcium channel ligands.^[3]

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 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.^[4]

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.^[5]

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. http://www.sciam.com/article.cfm?chanID=sa003&articleID=F9E196DB-E7F2-99DF-385C9F38537F58D6. 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.
^ 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 10 (4): 411–413. doi:10.1038/nn1860. PMID 17322876. http://med.stanford.edu/nbc/articles/7%20-%20Pharmacotherapy%20for%20Cognitive%20Impairment%20in%20a%20Mouse%20Model%20of%20Down%20Syndrome.pdf.
^ 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

English Journal

Behavioral and toxicological effects of propofol.

Gatch MB, Forster MJ.SourceDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Behavioural pharmacology.Behav Pharmacol.2011 Oct;22(7):718-22.
There is increasing concern about abuse of propofol, a widely-used surgical anesthetic and sedative that is currently not a controlled substance. The purpose of this study was to establish a rat model of the psychoactive effect of subanesthetic doses of propofol that could be useful for confirming a
PMID 21921842

Synthesis and anticonvulsant activity of new 1-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]pyrrolidine-2,5-diones.

Kami?ski K, Rzepka S, Obniska J.SourceDepartment of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
Bioorganic & medicinal chemistry letters.Bioorg Med Chem Lett.2011 Oct 1;21(19):5800-3. Epub 2011 Aug 6.
Twenty-two new 1-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]pyrrolidine-2,5-diones were synthesized and tested for anticonvulsant activity. Initial anticonvulsant screening was performed using standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens in mice. Several compou
PMID 21875804

Japanese Journal

EFHC1: A gene for juvenile myoclonic epilepsy

Yamakawa Kazuhiro
Epilepsy & Seizure 3(1), 121-124, 2010
… We recently generated Efhc1-deficient mouse and found that the mouse showed spontaneous myoclonus and increased susceptibility to a convulsant, pentylenetetrazol. …
NAID 130000255298

Effect of Brewer's Yeast-Induced Pyrexia on Aminophylline-Elicited Convulsions in Mice

Ochi Rika,Suemaru Katsuya,Kawasaki Hiromu,Araki Hiroaki
Acta Medica Okayama 63(5), 273-280, 2009-10
… The proconvulsant actions of the GABAA receptor antagonists picrotoxin (3-4mg/kg, i.p.) and pentylenetetrazol (40-60mg/kg, i.p.) were enhanced by Brewer's yeast. …
NAID 120002312799

Related Pictures

★リンクテーブル★

リンク元	「ペンテトラゾール」
拡張検索	「pentylenetetrazole」

「ペンテトラゾール」

Pentylenetetrazol
Systematic (IUPAC) name
	6,7,8,9-Tetrahydro-5H-tetrazolo(1,5-a)azepine
Clinical data
Pregnancy cat.	?
Legal status	?
Identifiers
CAS number	54-95-5
ATC code	R07AB03
PubChem	CID 5917
UNII	WM5Z385K7T
KEGG	D07409
ChEMBL	CHEMBL116943
Chemical data
Formula	C6H10N4
Mol. mass	138.171
	SMILES C12=NN=N[N]1CCCCC2;
(what is this?) (verify);

　　[★]

英: pentetrazol
同: ペンチレンテトラゾール pentylenetetrazol

痙攣薬

GABA-A遮断

特徴

構造

作用機序

ピクロトキシンと同様な作用機序
GABA_A受容体を拮抗阻害→膜の過分極↓→興奮性↑

薬理作用

漸進性、非同調的、間代性けいれん
てんかん脳波を誘発

動態

適応

注意

禁忌

副作用

相互作用

「pentylenetetrazole」

　　[★] ペンチレンテトラゾール

[sciam-0] JR Minkel (February 25, 2007). "Drug May Counteract Down Syndrome". Scientific American. http://www.sciam.com/article.cfm?chanID=sa003&articleID=F9E196DB-E7F2-99DF-385C9F38537F58D6. Retrieved 2007-03-20.

[1] Entry for Pentylenetetrazole in the MeSH database

[2] 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.

[3] 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 10 (4): 411–413. doi:10.1038/nn1860. PMID 17322876. http://med.stanford.edu/nbc/articles/7%20-%20Pharmacotherapy%20for%20Cognitive%20Impairment%20in%20a%20Mouse%20Model%20of%20Down%20Syndrome.pdf.

[4] 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

匿名

検索

案内

案内

pentylenetetrazol