Pentylenetetrazole: A review

• Published in: Neurochemistry international Vol. 180; p. 105841
• Main Authors: Monteiro, Álefe Brito, Alves, Alan Ferreira, Ribeiro Portela, Anne Caroline, Oliveira Pires, Hugo Fernandes, Pessoa de Melo, Mayara, Medeiros Vilar Barbosa, Nayana Maria, Bezerra Felipe, Cícero Francisco
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2024
• Subjects: Epileptic seizures; Epileptogenesis; Excitotoxicity; Preclinical model; Tetrazole; Epileptogenesis; Epileptic seizures; Tetrazole; Excitotoxicity; Preclinical model
• ISSN: 0197-0186; 1872-9754; 1872-9754
• DOI: 10.1016/j.neuint.2024.105841

Pentylenetetrazole (PTZ), a tetrazole derivative, is commonly used as a chemical agent to induce neurological disorders and replicate the characteristics of human epileptic seizures in animal models. This review offers a comprehensive analysis of the behavioral, neurophysiological, and neurochemical changes induced by PTZ. The epileptogenic and neurotoxic mechanisms of PTZ are associated with an imbalance between the GABAergic and glutamatergic systems. At doses exceeding 60 mg/kg, PTZ exerts its epileptic effects by non-competitively antagonizing GABAA receptors and activating NMDA receptors, resulting in an increased influx of cations such as Na+ and Ca2+. Additionally, PTZ promotes oxidative stress, microglial activation, and the synthesis of pro-inflammatory mediators, all of which are features characteristic of glutamatergic excitotoxicity. These mechanisms ultimately lead to epileptic seizures and neuronal cell death, which depend on the dosage and method of administration. The behavioral, electroencephalographic, and histological changes associated with PTZ further establish it as a valuable preclinical model for the study of epileptic seizures, owing to its simplicity, cost-effectiveness, and reproducibility.
•PTZ-induced seizures replicate human epileptic features in animal models.•PTZ's mechanism involves glutamate excitotoxicity, oxidative stress, and neuroinflammation.•The popularity of PTZ as a model is due to its simplicity, low cost, high reproducibility, and reliability.•PTZ models allow researchers to evaluate the antiepileptic potential of bioactive compounds.