Maximal electroshock seizure
(MES)
In the MES test, mice or rats
receive an electrical stimulus of sufficient intensity to induce maximal seizures
of their hind limbs, with tonic extension as the endpoint of the test
In the MES test,60Hz alternating
current is delivered for 0.2 second through corneal electrodes.
The test is easily conducted,
requires a minimal investment in equipment and technical expertise, and is well
standardized. Additionally,the epileptic activity is no longer contaminated by
the epileptogenic agent since it occurs only during application of the current.
Unfortunately, the animals can be
used only once.
6-Hz Seizure Test
Compounds are also screened for
their ability to block psychomotor seizures induced by a low-frequency (6 Hz),
long-duration (3 sec) stimulus delivered through corneal electrodes
6 Hz test demonstrates partial,
to complete resistance to the Na+ channel blockers, thus making the 6 Hz test
useful as an early identification and differentiation screen.
Compounds found to be effective
in this low-frequency (6 Hz), long-duration assay may therefore be effective in
the treatment of therapy-resistant partial seizures.
Subcutaneous Metrazol (sc Met)
Subcutaneous injection of the
convulsant Metrazol produces clonic seizures in laboratory animals.
The scMET test detects the
ability of a test compound to raise the seizure threshold of an animal and thus
protect it from exhibiting a clonic seizure in response to a normally
convulsant dose of Metrazol.
Animals are pretreated with
various doses of the test compound given by i.p. injection or through oral
dosing. At various times after dosing with the test compound, the dose of
Metrazol which will induce convulsions in 97% of animals is injected into a
loose fold of skin in the midline of the neck.
The animals are placed in
isolation cages to minimize stress and observed for the next 30 minutes for the
presence or absence of a seizure.
An episode of clonic spasms, approximately 3-5
seconds, of the fore and/or hindlimbs, jaws, or vibrissae is taken as the
endpoint.
Animals which do not meet this criterion are
considered protected
