Table 3.

Discriminatory properties toward AEDs and neuroprotectors of the MDDAS modulation model: an overview

Compounds	Main mode of action	MDDAS prevention test (anticonvulsant efficace doses)	MDDAS modulation test (modulation of MDDAS components)
			Latency	Wild running	Convulsion	Recovery
AEDs
Phenytoinergic  PHT	Neuronal voltage-dependent sodium channels	ED50 (24 mg/kg)		⇑⇑	⇓⇓	⇓⇓	⇓⇓⇓
CBZ		ED50 (25 mg/kg)
GABAergic  PB	Interaction with GABAA receptor– chloride ionophore	ED50 (13 mg/kg)	⇑	⇑	⇓	⇓
DZP	complex or	ED50 (0.09 mg/kg)
VPA	GABA metabolism	ED50 (70 mg/kg)
Ethosuximide  ESM	Interaction with calcium channels of type T	ED50 (73 mg/kg)	No effect	No effect	No effect	No effect
Neuroprotectors
WEB2170	Anti-PAF	10 mg/kg (no anticonvulsant activity at doses tested)	No effect	No effect	No effect	Suppression (100% reduction)
Melatonin	Free radical scavenger melatoninergic receptors	At non-anticonvulsant dose: 10 mg/kg	No effect	No effect	No effect	⇓
	GABAergic mechanisms(?)	At the anticonvulsant ED50: 60 mg/kg	⇑	⇑	⇓	⇓⇓
Neuroprotective potential of AEDs3-a
GABAergic
PB		ED0 (2.5 mg/kg)
DZP		ED0 (0.01 mg/kg)
VPA		ED0 (30 mg/kg)
ESM		ED0 (30 mg/kg)	No effect	No effect	No effect	No effect
PHT		ED0 (5 mg/kg)	⇑⇑	↓	↓	•
CBZ		ED0 (5 mg/kg)	⇑⇑	↓	No effect	⇓
Miscellaneous3-1002
Phenytoinergic
PHT		ED100 (80 mg/kg)
CBZ		ED100 (100 mg/kg)	No effect	No effect	No effect	No effect
ESM		ED100 (100 mg/kg)
GABAergic
PB		ED100 (50 mg/kg)	⇑	⇑	No effect	No effect
DZP		ED100 (0.5 mg/kg)
VPA		ED100 (100 mg/kg)

Anticonvulsant efficaces doses (ED) in the MDDAS prevention test are defined as follows: ED₅₀ values refer to doses of compounds preventing the convulsive component of MDDASs in 50% of test animals; ED₁₀₀ values refer to the lowest tested doses preventing the seizure component of MDDAS in 100% of test animals; and ED₀ values refer to the highest tested doses of compounds that do not reduce the percentage of convulsing animals. For general information on the main mode of action of AEDs, see MacDonald and Kelly (1995). Note that in practice in MDDAS modulation tests, ED₄₀–ED₄₅ instead of ED₅₀ doses of AEDs were used (see Table 2).

The symbols •, ↓, ⇓, ⇓⇓, and ⇓⇓⇓ signify a decrease in periods of <10%, between 10 and 25%, between 25 and 200%, between 200 and 500%, and >500%, respectively. The symbols ⇑ and ⇑⇑ signify an increase in time periods between 25 and 200% and between 200 and 500%.

^F3-a MDDAS testing of AEDs at non-anticonvulsant doses.

F3-1002:  MDDAS testing of AEDs at dose-preventing seizures in 100% of test animals.