Pentylenetetrazol Induced Seizure (PTZ)

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Epilepsy is a significant medical problem facing millions of people, most of who are not controlled by the current anticonvulsants on the market. Although several marketed anticonvulsants exist there remains a significant unmet medical need for better anticonvulsants with reduced liability.

Pentylenetetrazole (PTZ), a GABA receptor antagonist, is used to create a common chemically- induced seizure model. Amongst all animal models of seizure and epilepsy, the pentylenetetrazole-induced seizures are categorized as a model of generalized seizure (versus partial or focal seizure). It produces a myoclonic seizure that models absence (petit mal) seizures. As a generalized seizure model it has features that differentiate it from the MES Seizure model (also a model of generalized seizure).

When screening anticonvulsant candidates the PTZ model is an excellent tool for evaluating anti-seizure characteristics compared to a focal or partial seizure model (Psychomotor Seizure) such as the 6 Hz Model. Compounds that enhance GABAergic transmission are effective in ameliorating seizure activity in the PTZ epilepsy model

Latency to myoclonic and tonic hindlimb seizure in mice pre-treated with diazepam before PTZ administration.

After a 24-hour fast, mice were injected with vehicle or Diazepam (30mg/kg) 15 minutes prior to PTZ administration. After PTZ was administered, the time until the first whole body clonus event and time to the tonic-hind limb extension were calculated.

(A-B) Diazepam significantly delayed the onset of the myoclonic seizure and the onset of the tonic hindlimb extensor response until at least the five minute time-out.
Data are mean ± SEM; **p<0.01, ***p<0.001 compared to vehicle.

The PTZ Seizure model can be conducted in either rats or mice. Most studies can be completed as a one-day procedure. Group sizes are generally 8-12 animals.