Thyrotropin-releasing hormone in the treatment of intractable epilepsy

Intractable seizures remain a significant therapeutic challenge despite current advances in the treatment of epilepsy. Thyrotropin-releasing hormone, the first neuroendocrine releasing factor to be isolated and fully characterized, was also the first releasing factor investigated as a possible neurotransmitter/neuromodulator outside the hypothalamus. Basic and clinical research has revealed a distinct neuroanatomic distribution and a neurochemical role for thyrotropin-releasing hormone in seizure modulation. Thyrotropin-releasing hormone and selected analogs were reported to have antiepileptic effects in several animal seizure paradigms, including kindling and electroconvulsive shock. Clinically, thyrotropin-releasing hormone treatment has been reported to be efficacious in such intractable epilepsies as infantile spasms, Lennox-Gastaut syndrome, myoclonic seizures, and other generalized and refractory partial seizures. Herein, we review evidence that suggests that thyrotropin-releasing hormone and selected thyrotropin-releasing hormone analogs may represent a new class of novel antiepileptic drugs, namely, antiepileptic neuropeptides and provide insights into potential new treatments for the intractable epilepsies.