The Anticonvulsant Effect of TRH Analog (DN-1417) and TRH-T

純, 中村; 直尚, 内村; 茂人, 山田; 哲之, 堤; 賢治, 石橋; 秀樹, 小島; 和豊, 稲永

doi:10.3805/jjes.2.76

Cited by 2 publications

(2 citation statements)

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“…The mechanism underlying the anticonvulsant action of DN-1417 is not clearly understood. Previous experimental studies suggested a possible role of serotonin (Nagai et al, 1985) or somatostatin (Nagaki and Kato., 1985), but not GABA (Nakamura et al, 1984). Some reports suggest dopaminergic participation, however (Nakamura et al, 1984;Sat0 et al, 1986).…”

Section: Discussionmentioning

confidence: 96%

“…Previous experimental studies suggested a possible role of serotonin (Nagai et al, 1985) or somatostatin (Nagaki and Kato., 1985), but not GABA (Nakamura et al, 1984). Some reports suggest dopaminergic participation, however (Nakamura et al, 1984;Sat0 et al, 1986). Dopamine release in the striatum and the nucleus accumbens increases with TRH (Bennett et al, 1981;Miya-mot0 et al, 1981) and DN-1417(Sato et al, 1986.…”

Section: Discussionmentioning

confidence: 96%

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Effect of DN‐1417 on Photosensitivity and Cortically Kindled Seizure in Senegalese Baboons, Papio papio

et al. 1991

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The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4-5 days. A study of the transcallosal response also showed a long-lasting attenuation of the early positive wave (P1) amplitude (peak latency, 5-10 ms) elicited by a single stimulus after cisternal injection of DN-1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Effect of DN‐1417 on Photosensitivity and Cortically Kindled Seizure in Senegalese Baboons, Papio papio

et al. 1991

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Clinical Study of Oral Administration of DN‐1417, a TRH Analog, in Patients with Intractable Epilepsy

et al. 1989

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An open dose-finding trial of orally administered DN-1417 was undertaken to investigate dose, efficacy, and adverse reactions. One hundred ninety patients, with epilepsy resistant to conventional drug treatment, were randomly allocated to two treatment groups of low dose (20 mg/day for adult) and high dose (80 mg/day for adult). Medication was given while fasting, once a day, for 8 weeks. If at the end of the first 4-week treatment period the patient had a satisfactory response, the dose was doubled. Patient response was assessed by global improvement rating (GIR) based on changes in seizure frequency, EEG findings, and nonparoxysmal clinical manifestations. The responses assessed by GIR was "slightly to markedly improved" in 48% of the patients with low-dose treatment and 55% with high-dose treatment. There was no clear dose-related difference between the two treatments. In patients with Lennox-Gastaut syndrome having no history of West syndrome, the rate of response assessed by GIR was found to be slightly dose-related (low dose, 61%; high dose, 73%).

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The Anticonvulsant Effect of TRH Analog (DN-1417) and TRH-T

Cited by 2 publications

References 19 publications

Effect of DN‐1417 on Photosensitivity and Cortically Kindled Seizure in Senegalese Baboons, Papio papio

Effect of DN‐1417 on Photosensitivity and Cortically Kindled Seizure in Senegalese Baboons, Papio papio

Clinical Study of Oral Administration of DN‐1417, a TRH Analog, in Patients with Intractable Epilepsy

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