Pentylenetetrazol, also known as pentylenetetrazole, leptazol, metrazol, pentetrazol (INN), pentamethylenetetrazol, Corazol, Cardiazol, Deumacard, or PTZ, is a drug formerly used as a circulatory and respiratory stimulant. High doses cause convulsions, as discovered by Hungarian-American neurologist and psychiatrist Ladislas J. Meduna in 1934. It has been used in convulsive therapy, and was found to be effective—primarily for depression—but side effects such as uncontrolled seizures were difficult to avoid.[1] In 1939, pentylenetetrazol was replaced by electroconvulsive therapy, which is easier to administer, as the preferred method for inducing seizures in England's mental hospitals. In the US, its approval by the Food and Drug Administration was revoked in 1982.[2] It is used in Italy as a cardio-respiratory stimulant in combination with codeine in a cough suppressant drug.[3]
The mechanism of pentylenetetrazol is not well understood, and it may have multiple mechanisms of action. 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 picrotoxin binding site on the GABA-A receptor complex. Many GABA-A ligands, such as the sedatives diazepam and phenobarbital, are effective anticonvulsants, but presumably pentylenetetrazol has the opposite effect when it binds to the GABA-A receptor.[4]
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.[5]
Research
Pentylenetetrazol has been used experimentally to study seizure phenomena and to identify pharmaceuticals that may control seizure susceptibility. For instance, researchers can induce status epilepticus in animal models. Pentylenetetrazol is also a prototypical anxiogenic drug and has been extensively used 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 channelligands.[6]
^Read, Charles F. (1940). "Consequences of metrazol shock therapy". American Journal of Psychiatry. 97 (3): 667–76. doi:10.1176/ajp.97.3.667.
^Minkel JR (February 25, 2007). "Drug May Counteract Down Syndrome". Scientific American. Retrieved 2007-03-20.
^"Cardiazol-Paracodina". Agenzia Italiana del Farmaco.
^Squires RF, Saederup E, Crawley JN, Skolnick P, Paul SM (1984). "Convulsant potencies of tetrazoles are highly correlated with actions on GABA / benzodiazepine / picrotoxin receptor complexes in brain". Life Sci. 35 (14): 1439–44. doi:10.1016/0024-3205(84)90159-0. PMID 6090836.
^Papp A, Fehér O, Erdélyi L (1987). "The ionic mechanism of the pentylenetetrazol convulsions". Acta Biol. Hung. 38 (3–4): 349–61. PMID 3503442.
^Jung ME, Lal H, Gatch MB (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. S2CID 26055062.
January 31, 2023
pentylenetetrazol, also, known, pentylenetetrazole, leptazol, metrazol, pentetrazol, pentamethylenetetrazol, corazol, cardiazol, deumacard, drug, formerly, used, circulatory, respiratory, stimulant, high, doses, cause, convulsions, discovered, hungarian, ameri. Pentylenetetrazol also known as pentylenetetrazole leptazol metrazol pentetrazol INN pentamethylenetetrazol Corazol Cardiazol Deumacard or PTZ is a drug formerly used as a circulatory and respiratory stimulant High doses cause convulsions as discovered by Hungarian American neurologist and psychiatrist Ladislas J Meduna in 1934 It has been used in convulsive therapy and was found to be effective primarily for depression but side effects such as uncontrolled seizures were difficult to avoid 1 In 1939 pentylenetetrazol was replaced by electroconvulsive therapy which is easier to administer as the preferred method for inducing seizures in England s mental hospitals In the US its approval by the Food and Drug Administration was revoked in 1982 2 It is used in Italy as a cardio respiratory stimulant in combination with codeine in a cough suppressant drug 3 PentylenetetrazolClinical dataTrade namesMetrazol othersATC codeR07AB03 WHO IdentifiersIUPAC name 6 7 8 9 Tetrahydro 5H tetrazolo 1 5 a azepineCAS Number54 95 5 YPubChem CID5917ChemSpider5704 NUNIIWM5Z385K7TKEGGD07409 NChEBICHEBI 34910 NChEMBLChEMBL116943 NCompTox Dashboard EPA DTXSID7041091ECHA InfoCard100 000 200Chemical and physical dataFormulaC 6H 10N 4Molar mass138 174 g mol 13D model JSmol Interactive imageSMILES C1CCc2nnnn2CC1InChI InChI 1S C6H10N4 c1 2 4 6 7 8 9 10 6 5 3 1 h1 5H2 NKey CWRVKFFCRWGWCS UHFFFAOYSA N N N Y what is this verify Contents 1 Mechanism 2 Research 3 See also 4 ReferencesMechanism EditThe mechanism of pentylenetetrazol is not well understood and it may have multiple mechanisms of action 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 picrotoxin binding site on the GABA A receptor complex Many GABA A ligands such as the sedatives diazepam and phenobarbital are effective anticonvulsants but presumably pentylenetetrazol has the opposite effect when it binds to the GABA A receptor 4 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 5 Research EditPentylenetetrazol has been used experimentally to study seizure phenomena and to identify pharmaceuticals that may control seizure susceptibility For instance researchers can induce status epilepticus in animal models Pentylenetetrazol is also a prototypical anxiogenic drug and has been extensively used 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 6 See also EditList of investigational sleep drugs GABAA receptor negative allosteric modulator GABAA receptor LigandsReferences Edit Read Charles F 1940 Consequences of metrazol shock therapy American Journal of Psychiatry 97 3 667 76 doi 10 1176 ajp 97 3 667 Minkel JR February 25 2007 Drug May Counteract Down Syndrome Scientific American Retrieved 2007 03 20 Cardiazol Paracodina Agenzia Italiana del Farmaco Squires RF Saederup E Crawley JN Skolnick P Paul SM 1984 Convulsant potencies of tetrazoles are highly correlated with actions on GABA benzodiazepine picrotoxin receptor complexes in brain Life Sci 35 14 1439 44 doi 10 1016 0024 3205 84 90159 0 PMID 6090836 Papp A Feher O Erdelyi L 1987 The ionic mechanism of the pentylenetetrazol convulsions Acta Biol Hung 38 3 4 349 61 PMID 3503442 Jung ME Lal H Gatch MB 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 S2CID 26055062 Retrieved from https en wikipedia org w index php title Pentylenetetrazol amp oldid 1112210003, wikipedia, wiki, book, books, library,
