Involvement of thyrotropin-releasing hormone (TRH) neural system of the brain in pentylenetetrazol-induced seizures

Ogawa, Norio; Hirose, Yukiko; Mori, Akitane; Kajita, Saburo; Sato, Mitsumoto

doi:10.1016/0167-0115(85)90066-7

Cited by 35 publications

(9 citation statements)

References 18 publications

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“…[17, 50] Therefore, selected compounds 21 a – c and 22 a , b were evaluated for anticonvulsant activity against PTZ-induced seizures in mice according to a method described earlier. [51] The compounds were dissolved in normal saline and administered at doses of 10 μmol kg −1 i.v.…”

Section: Resultsmentioning

confidence: 99%

“…TRH is known to provide protection against seizures induced by kainic acid and glutamate, supporting the observed potency of TRH analogues in PTZ-induced seizures. [50, 53] TRH was also shown to increase GABA release, and this may contribute to its antiepileptic action. [54] However, additional studies are required to explore the exact mechanism of action of these analogues.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin‐Releasing Hormone (TRH) Analogues

et al. 2011

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As part of our search for selective and CNS-active thyrotropin-releasing hormone (TRH) analogues, we synthesized a set of 44 new analogues in which His and pGlu residues were modified or replaced. The analogues were evaluated as agonists at TRH-R1 and TRH-R2 in cells in vitro, and in vivo in mice for analeptic and anticonvulsant activities. Several analogues bound to TRH-R1 and TRH-R2 with good to moderate affinities, and are full agonists at both receptor subtypes. Specifically, analogue 21 a (R = CH3) exhibited binding affinities (Ki values) of 0.17 μM for TRH-R1 and 0.016 μM for TRH-R2; it is 10-fold less potent than TRH in binding to TRH-R1 and equipotent with TRH in binding to TRH-R2. Compound 21 a, the most selective agonist, activated TRH-R2 with a potency (EC50 value) of 0.0021 μM, but activated TRH-R1 at EC50 = 0.05 μM, and exhibited 24-fold selectivity for TRH-R2 over TRH-R1. The newly synthesized TRH analogues were also evaluated in vivo to assess their potencies in antagonism of barbiturate-induced sleeping time, and several analogues displayed potent analeptic activity. Specifically, analogues 21 a,b and 22 a,b decreased sleeping time by nearly 50 % more than TRH. These analogues also displayed potent anticonvulsant activity and provided significant protection against PTZ-induced seizures, but failed to provide any protection in MES-induced seizures at 10 μmol kg−1. The results of this study provide evidence that TRH analogues that show selectivity for TRH-R2 over TRH-R1 possess potent CNS activity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin‐Releasing Hormone (TRH) Analogues

et al. 2011

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“…This result is similar to the effects of TRH following intracerebral administration where seizure duration was significantly attenuated in fully kindled animals (Wan et al, 1998), as well as, during kindling development (Kubek et al, 1998). TRH has been shown extensively to act as an anticonvulsant in humans (Takeuchi et al, 2001; Kubek and Garg, 2002) and several animal seizure models (Ogawa et al, 1985; Sakai et al, 1991; Momiyama et al, 1996; Jaworska‐Feil et al, 1999; Jaworska‐Feil et al, 2001) indicating a potentially novel neuropeptide anticonvulsant.…”

Section: Discussionmentioning

confidence: 99%

Intranasal Delivery of a Thyrotropin‐Releasing Hormone Analog Attenuates Seizures in the Amygdala‐Kindled Rat

Veronesi

Kubek

2007

Epilepsia

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“…Thyrotropin-releasing hormone has received attention as an endogenous antiepileptic substance (Ogawa et al, 1985;. Thyrotropin-releasing hormone is involved in the formation, release, and metabolism of catecholamines and acetylcholine.…”

mentioning

confidence: 99%

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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Involvement of thyrotropin-releasing hormone (TRH) neural system of the brain in pentylenetetrazol-induced seizures

Cited by 35 publications

References 18 publications

Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin‐Releasing Hormone (TRH) Analogues

Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin‐Releasing Hormone (TRH) Analogues

Intranasal Delivery of a Thyrotropin‐Releasing Hormone Analog Attenuates Seizures in the Amygdala‐Kindled Rat

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

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