Pentylenetetrazol

Overview

Pentylenetetrazol (PTZ), or pentylenetetrazole, also known as pentetrazol (INN (International Nonproprietary Name)) and sold under the brand name Metrazol, 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 in treating depression, but side effects, such as uncontrolled seizures, were difficult to avoid. In 1939, pentylenetetrazol was replaced by electroconvulsive therapy (ECT), which is easier to administer, as the preferred method for inducing seizures in England's mental hospitals. In the US, pentylenetetrazol's approval by the Food and Drug Administration (FDA) was revoked in 1982. It is used in Italy as a cardio-respiratory stimulant in combination with dihydrocodeine in a cough suppressant drug.[1][2][3] WP

Drug class

GABAA receptor antagonist Convulsant Anxiogenic Stimulant Wakefulness-promoting agent WP

From the Wikipedia article's infobox.

Risks and side effects

Side effects

Pentylenetetrazol is anxiogenic and has been known to induce severe anxiety in humans.[4] WP

Pharmacology

Mechanism of action

The mechanism of pentylenetetrazol is not well-understood, and it may have multiple actions. 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 GABAA receptor. Many GABAA receptor ligands, such as diazepam and phenobarbital, are effective anticonvulsants, but pentylenetetrazol presumably has the opposite effect when it binds to the GABAA receptor.[5] WP

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.[6] WP

Research

Research

Pentylenetetrazol has been used experimentally to study seizure phenomena and to identify pharmaceuticals that may control seizure susceptibility. Recent preclinical work has used pentylenetetrazol to evaluate experimental antiseizure compounds. For example, the synthetic molecule BICS01 showed no protective effect against PTZ induced seizures in mice despite suppressing epileptiform activity in hippocampal slice models 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.[7][8] WP

Pentylenetetrazol is being studied as a wakefulness-promoting agent in the treatment of idiopathic hypersomnia and narcolepsy.[9][10] WP

Chemistry

Formula

C6H10N4 PC

CAS number

54-95-5 PC

Molar mass (g/mol)

138.17 PC

IUPAC name (computed by PubChem)

6,7,8,9-tetrahydro-5H-tetrazolo[1,5-a]azepine PC

SMILES

C1CCC2=NN=NN2CC1 PC

InChIKey

CWRVKFFCRWGWCS-UHFFFAOYSA-N PC

PubChem CID

5917

IUPAC name

6,7,8,9-tetrahydro-5H-tetrazolo(1,5-a)azepine WP

Mixing

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Read CF. Consequences of metrazol shock therapy. American Journal of Psychiatry. 1940. doi:10.1176/ajp.97.3.667
2. Other Minkel JR. Drug May Counteract Down Syndrome. February 25, 2007
3. Other Cardiazol-Paracodina
4. Journal / agency Durant C, Christmas D, Nutt D. Current Topics in Behavioral Neurosciences. 2009. doi:10.1007/7854_2009_8 · PMID 21309115
5. Journal / agency Squires RF, Saederup E, Crawley JN, Skolnick P, Paul SM. Convulsant potencies of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain. Life Sciences. October 1984. doi:10.1016/0024-3205(84)90159-0 · PMID 6090836
6. Journal / agency Papp A, Fehér O, Erdélyi L. The ionic mechanism of the pentylenetetrazol convulsions. Acta Biologica Hungarica. 1987. PMID 3503442
7. Journal / agency Morris G, Heiland M, Lamottke K, Guan H, Hill TD, Zhou Y, Zhu Q, Schorge S, Henshall DC. BICS01 Mediates Reversible Anti-seizure Effects in Brain Slice Models of Epilepsy. Frontiers in Neurology. 2022. doi:10.3389/fneur.2021.791608 · PMID 35069421 · PMC8770400
8. Journal / agency Jung ME, Lal H, Gatch MB. The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: recent developments. Neuroscience and Biobehavioral Reviews. June 2002. doi:10.1016/S0149-7634(02)00010-6 · PMID 12204190
9. Journal / agency Pentylenetetrazole - Balance Therapeutics. 28 June 2020
10. Journal / agency Takahashi T, Noriaki S, Matsumura M, Li C, Takahashi K, Nishino S. Advances in pharmaceutical treatment options for narcolepsy. Expert Opinion on Orphan Drugs. 3 October 2018. doi:10.1080/21678707.2018.1521267

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.