PENTETRAZOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H10N4
Molecular Weight	138.1704
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CCN2N=NN=C2CC1

InChI

InChIKey=CWRVKFFCRWGWCS-UHFFFAOYSA-N

InChI=1S/C6H10N4/c1-2-4-6-7-8-9-10(6)5-3-1/h1-5H2

HIDE SMILES / InChI

Molecular Formula	C6H10N4
Molecular Weight	138.1704
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/mesh/68010433 | http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2016/01/WC500199415.pdf

Pentetrazol (pentylenetetrazole, BTD-001) is a pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive gamma-aminobutyric acid (GABA) antagonist. Pentetrazol (pentylenetetrazole) has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. GABA is thought to play a role in promoting sleep and its function is believed to be elevated in idiopathic hypersomnia. By blocking GABA’s function, pentetrazol (pentylenetetrazole, BTD-001) is expected to reduce excessive daytime sleepiness.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; alpha-1/beta-2/gamma-2 28 Target ID: CHEMBL2095172 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11504794	Inhibitor 8504		0.98 mM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Idiopathic hypersomnia 1 Sources: https://clinicaltrials.gov/ct2/show/study/NCT02512588	Primary		Phase II 1147	Unknown Approved Use Unknown
Narcolepsy without cataplexy 3 Sources: https://clinicaltrials.gov/ct2/show/study/NCT02512588	Primary		Phase II 1147	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
32 mg 3 times / day multiple, oral Recommended Dose: 32 mg, 3 times / day Route: oral Route: multiple Dose: 32 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 1-7 Health Status: unhealthy Age Group: 1-7 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	Other AEs: Convulsive seizure, Weight gain... Other AEs: Convulsive seizure (1 patient) Weight gain (16 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
130 mg 3 times / day multiple, oral Recommended Dose: 130 mg, 3 times / day Route: oral Route: multiple Dose: 130 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 4-11 Health Status: unhealthy Age Group: 4-11 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	Other AEs: Convulsive seizure, Weight gain... Other AEs: Convulsive seizure (1 patient) Weight gain (21 patient) Weight loss (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
97 mg 3 times / day multiple, oral Recommended Dose: 97 mg, 3 times / day Route: oral Route: multiple Dose: 97 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 5-17 Health Status: unhealthy Age Group: 5-17 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	Disc. AE: Behavior disorder... AEs leading to discontinuation/dose reduction: Behavior disorder (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
200 mg 4 times / day multiple, oral Recommended Dose: 200 mg, 4 times / day Route: oral Route: multiple Dose: 200 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4932747/	unhealthy, 65-82 Health Status: unhealthy Age Group: 65-82 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4932747/	Other AEs: Weight loss... Other AEs: Weight loss (9 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/4932747/
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516	unhealthy, 65-93 Health Status: unhealthy Age Group: 65-93 Sex: M+F Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516	Disc. AE: Dizziness, Drowsiness... AEs leading to discontinuation/dose reduction: Dizziness (2 patients) Drowsiness (1 patient) Nausea (1 patient) Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516

AEs

AE	Significance	Dose	Population
Convulsive seizure	1 patient	32 mg 3 times / day multiple, oral Recommended Dose: 32 mg, 3 times / day Route: oral Route: multiple Dose: 32 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 1-7 Health Status: unhealthy Age Group: 1-7 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
Weight gain	16 patients	32 mg 3 times / day multiple, oral Recommended Dose: 32 mg, 3 times / day Route: oral Route: multiple Dose: 32 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 1-7 Health Status: unhealthy Age Group: 1-7 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
Convulsive seizure	1 patient	130 mg 3 times / day multiple, oral Recommended Dose: 130 mg, 3 times / day Route: oral Route: multiple Dose: 130 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 4-11 Health Status: unhealthy Age Group: 4-11 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
Weight gain	21 patient	130 mg 3 times / day multiple, oral Recommended Dose: 130 mg, 3 times / day Route: oral Route: multiple Dose: 130 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 4-11 Health Status: unhealthy Age Group: 4-11 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
Weight loss	4 patients	130 mg 3 times / day multiple, oral Recommended Dose: 130 mg, 3 times / day Route: oral Route: multiple Dose: 130 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 4-11 Health Status: unhealthy Age Group: 4-11 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
Behavior disorder	3 patients Disc. AE	97 mg 3 times / day multiple, oral Recommended Dose: 97 mg, 3 times / day Route: oral Route: multiple Dose: 97 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/	unhealthy, 5-17 Health Status: unhealthy Age Group: 5-17 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/13457651/
Weight loss	9 patients	200 mg 4 times / day multiple, oral Recommended Dose: 200 mg, 4 times / day Route: oral Route: multiple Dose: 200 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4932747/	unhealthy, 65-82 Health Status: unhealthy Age Group: 65-82 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4932747/
Drowsiness	1 patient Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516	unhealthy, 65-93 Health Status: unhealthy Age Group: 65-93 Sex: M+F Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516
Nausea	1 patient Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516	unhealthy, 65-93 Health Status: unhealthy Age Group: 65-93 Sex: M+F Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516
Dizziness	2 patients Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516	unhealthy, 65-93 Health Status: unhealthy Age Group: 65-93 Sex: M+F Sources: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490516

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP450 59

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 59	substrate 4014 Sources: https://patents.google.com/patent/WO2012151343A1/en	likely

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:34910	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:34910
ChemicalBook	CB4248615	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4248615
eMolecules	593721	https://www.emolecules.com/cgi-bin/more?vid=593721
MolPort	MolPort-001-783-580	https://www.molport.com/shop/molecule-link/MolPort-001-783-580
ZINC	ZINC000000001905	http://zinc15.docking.org/substances/ZINC000000001905

PubMed

Title	Date	PubMed
Neonatal toluene exposure selectively alters sensitivity to different chemoconvulsant drugs in juvenile rats.	2002-11	12213539
Effects of pentylenetetrazol-induced kindling of seizures on rat emotional behavior and brain monoaminergic systems.	2002-11	12213531
Single mutation (A162H) in human cardiac troponin I corrects acid pH sensitivity of Ca2+-regulated actomyosin S1 ATPase.	2002-09-20	12151382
Effect of CGP39551 administration on the kindling of ethanol-withdrawal seizures.	2002-09	12202962
Lithium and KB-R7943 effects on mechanics and energetics of rat heart muscle.	2002-09	12193213
Anxiolytic and anticonvulsive activity of Sesbania grandiflora leaves in experimental animals.	2002-08	12203267
GABA-A receptor complex and memory processes.	2002-08	12171575
Synthesis and anticonvulsant activity of enaminones. 4. Investigations on isoxazole derivatives.	2002-08	12161061
Increase of nucleotidase activities in rat blood serum after a single convulsive injection of pentylenetetrazol.	2002-07	12103446
Anticonvulsant profile and mechanism of action of propranolol and its two enantiomers.	2002-07	12076101
Anticonvulsive activity of Butea monosperma flowers in laboratory animals.	2002-07	12062587
GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.	2002-06-28	12106804
The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: recent developments.	2002-06	12204190
Possible anxiolytic effects of ivermectin in rats.	2002-06	12184502
Do preclinical seizure models preselect certain adverse effects of antiepileptic drugs.	2002-06	12151115
Anticonvulsant and sedative effects of Salvadora persica L. stem extracts.	2002-06	12112302
Pentylenetetrazol-induced recurrent seizures in rat pups: time course on spatial learning and long-term effects.	2002-06	12060014
Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility.	2002-05-01	11978855
Congenic mapping of alcohol and pentobarbital withdrawal liability loci to a <1 centimorgan interval of murine chromosome 4: identification of Mpdz as a candidate gene.	2002-05-01	11978849
Developmental lead exposure differentially alters the susceptibility to chemoconvulsants in rats.	2002-05-01	11960677
Anxiogenic properties of Ptychopetalum olacoides Benth. (Marapuama).	2002-05	12164265
Changes of cortical epileptic afterdischarges under the influence of convulsant drugs.	2002-05	12121812
Nitric oxide (NO) and convulsions induced by pentylenetetrazol.	2002-05	12076982
Cardiovascular protection by alcohol and polyphenols: role of nitric oxide.	2002-05	12074966
The effects of ACTH and adrenocorticosteroids on seizure susceptibility in 15-day-old male rats.	2002-05	12009770
GABAA-benzodiazepine receptor complex ligands and stress-induced hyperthermia in singly housed mice.	2002-05	11900786
Seizure-mediated accumulation of the beta subunit of Ca2+/calmodulin-dependent protein kinase II in nuclei of mouse brain cells.	2002-04-12	11897160
Effects of NG-nitro-L-arginine methyl ester, 7-nitro indazole, and agmatine on pentylenetetrazol-induced discriminative stimulus in Long-Evans rats.	2002-04	11999909
Proconvulsant effects of high doses of venlafaxine in pentylenetetrazole-convulsive rats.	2002-04	11960197
2-Chloroadenosine, a preferential agonist of adenosine A1 receptors, enhances the anticonvulsant activity of carbamazepine and clonazepam in mice.	2002-04	11872335
Selectivity of the protective effects of dihydropyridine calcium channel antagonists against the ethanol withdrawal syndrome.	2002-03-15	11879801
Effects of antisense glutamic acid decarboxylase oligodeoxynucleotide on epileptic rats induced by pentylenetetrazol.	2002-03	11940381
Effects of lorazepam treatment for multiple ethanol withdrawals in mice.	2002-03	11923591
Anticonvulsant profile and teratogenicity of N-methyl-tetramethylcyclopropyl carboxamide: a new antiepileptic drug.	2002-02	11903457
Is glutamine beneficial in ischemic heart disease?	2002-02	11844641
The effects of callosal agenesis on the susceptibility to seizures elicited by pentylenetetrazol in BALB/cCF mice.	2002-01-29	11812512
[A novel model of perfused rat brain with intact nervous system].	2002-01	11808205
Behavior and physiology of mice lacking the GABAA-receptor delta subunit.	2002	12121286
Stimulation of gene expression of NeuroD-related factor in the mouse brain following pentylenetetrazol-induced seizures.	2001-12-30	11750069
Effects of ketoconazole on oestrus cycle and convulsant action of pentylenetetrazol in mice.	2001-12	11903957
KJ Smith, M Theal, A Mulji. Pericarditis presenting and treated as an acute anterospetal myocardial infarction. Can J Cardiol 2001;17(7):815-817.	2001-12	11780612
Low doses of AMPA exert anticonvulsant effects on pentylenetetrazol-kindled seizures.	2001-11-10	11701215
Morphological alterations of neurons and astrocytes and changes in emotional behavior in pentylenetetrazol-kindled rats.	2001-11-10	11701200
Re: Morales, FJ, Montemayor T, Martínez A. Shuttle versus six-minute walk test in the prediction of outcome in chronic heart failure. Int J Cardiol 2000;76: 101-105.	2001-10-26	11676392
Comparison of the anticonvulsant efficacies and neurotoxic effects of valproic acid, phenytoin, and the ketogenic diet.	2001-10	11737171
Myectomy for hypertrophic obstructive cardiomyopathy after failed alcohol septal ablation: Clinicopathological correlations. Can J Cardiol 2001;17:197-202.	2001-10	11706838
Effects of angiotensin III and angiotensin IV on pentylenetetrazol seizure susceptibility (threshold and kindling): interaction with adenosine A(1) receptors.	2001-09-15	11704344
Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats.	2001-09-14	11585590
Neurobehavioural study of subchronic administration of oxydemeton-methyl (insecticide and acaricide) in rats.	2001-07	11881572
Levetiracetam: the preclinical profile of a new class of antiepileptic drugs?	2001	11564119

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

In rat alpha1/beta2/gamma2 gamma-aminobutyric acid (GABA) type A receptors, pentetrazol inhibited GABA-activated Cl(-) current in a concentration-dependent, voltage-independent manner, with an IC50 of 0.62 +/- 0.13 mM. The mechanism of inhibition appeared competitive with respect to GABA in both rat and human alpha1/beta2/gamma2 receptors. Varying subunit configuration (change or lack of alpha subunit isoform or lack of gamma2 subunit) had modest effects on pentetrazol-induced inhibition, as evidenced by comparable IC50 values (0.6-2.2 mM) in all receptor configurations tested. Using a one-site model for pentetrazol interaction with alpha1/beta2/gamma2 receptors, the association rate (k(+1)) was found to be 1.14 x 10^3 M(-1)s(-1) and the dissociation rate (k(-1)) was 0.476 s(-1), producing a functional Kd of 0.418 mM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:16:56 GMT 2025` Edited by `admin` on `Mon Mar 31 18:16:56 GMT 2025`
Record UNII	WM5Z385K7T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PENTETRAZOL

Official Name

English

PENTYLENETETRAZOL

Preferred Name

English

CORYVET

Brand Name

English

PENTYLENETETRAZOLE [MI]

Common Name

English

pentetrazol [INN]

Common Name

English

CENAZOL

Common Name

English

CORAZOLE

Common Name

English

KORAZOLE

Common Name

English

NSC-66489

Code

English

Pentetrazol [WHO-DD]

Common Name

English

KORAZOL

Common Name

English

CARDIOZOL

Common Name

English

NSC-5729

Code

English

LEPTAZOL

Common Name

English

6,7,8,9-TETRAHYDRO-5H-TETRAZOLOAZEPINE

Common Name

English

PENTAMETHYLENETETRAZOLE

Common Name

English

METRAZOL

Brand Name

English

LEPTAZOLE

Common Name

English

CORANORMOL

Common Name

English

PENTETRAZOL [MART.]

Common Name

English

METRAZOLE

Common Name

English

CARDIAZOL

Brand Name

English

PENTYLENETETRAZOLE

Common Name

English

PENTYLENETETRAZOL [VANDF]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/15/1569