Long-term antiepileptic effects of chronic intake of CNK-602A, a thyrotropin-releasing hormone analogue, on spontaneously epileptic rats

Summary: Spontaneously epileptic rats (SER), which represent a double mutation (zi/zi, tm/tm), spontaneously exhibit both tonic and absence-like seizures. We examined the long-term effects of a thyrotropin-releasing hormone (TRH) analogue, CNK-602A, acute administration of which was effective in inhibiting both types of seizures in SER, to determine if this agent could be used to treat epilepsy for long periods. Food pellets containing 0.001% CNK-602A were given ad libitum to SER from age 7 weeks. CNK–602A significantly inhibited tonic convulsions and prolonged survival. There were no alterations in body weight or plasma levels of triiodotyronine (T3) and thyroxine (T4). These findings indicate that chronic intake of CNK-602A in a dose that does not affect plasma levels of T3 and T4 inhibits tonic convulsions in SER and suggest that this drug may be an effective treatment for convulsive seizures in patients with epilepsy.