Taltirelin. Tanabe Seiyaku.

Taltirelin is a synthetic thyrotropin-releasing hormone (TRH) analog, under development by Tanabe Seiyaku for the treatment of neurodegenerative diseases. A new drug application (NDA) has been filed in Japan for the treatment of spinocerebellar disease (SCD) and is under review. Data suggest that taltirelin enhances dopamine neurotransmission, although this has been questioned. Taltirelin potentiates acetylcholine (ACh)-induced neuronal excitation in rat cerebral cortex neurons and inhibits high concentration AChinduced desensitization of neuronal excitation. TRH receptors have been located in several parts of the rat brain, including the pituitary, hypothalamus, and brain stem. These data provide support for the claim that taltirelin may have a potential benefit in dementia, which is consistent with limited clinical data. Taltirelin has been shown to be more potent and longer acting than TRH in increasing the amplitude of spinal reflex potentials and withdrawal flexor reflexes in spinal rats after iv administration. The compound is also active after intraduodenal administration, in contrast to TRH, indicating its potential for the treatment of spinal functional disorders. Analysts at Yamaichi had predicted that taltirelin would be launched in Japan in 1998; this was optimistic, though the new drug application is currently under review. Additionally, their prediction was of peak annual sales of less than 5 billion Yen; however taltirelin has been designated as an orphan drug in Japan.