TRH receptor agonists ameliorate 3-acetylpyridine-induced ataxia through NMDA receptors in rats.

Abstract

The effects of thyrotropin-releasing hormone (TRH) receptor agonists were examined on 3-acetylpyridine-induced cerebellar ataxia in rats. 3-acetylpyridine markedly decreased the maximal height of vertical jump, accompanied by motor incoordination. Both TA-0910 ((-)-N-[(S)-hexahydro-1-methyl-2,6-dioxo-4-pyrimidinylcarbonyl]-L- histidyl-L-prolinamide tetrahydrate; 0.3-3 mg/kg), a novel TRH analog, and TRH (10 and 30 mg/kg) significantly increased the suppressed maximal height of vertical jump after single intraperitoneal administration. The effects of these drugs reached a maximum at 1 h and disappeared 24 h after administration. Both the TA-0910 (1 mg/kg)- and TRH (10 mg/kg)-induced increases in the maximal height of vertical jump were completely counteracted by pretreatment with i.p. injected MK-801 (10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate; 0.1 mg/kg), an NMDA receptor antagonist. Neither bicuculline, muscimol, baclofen, cyproheptadine nor prazosin affected the effect of the TRH receptor agonists. In conclusion, TA-0910 is more potent than TRH in ameliorating cerebellar functional disorders. The anti-ataxic effects of these TRH receptor agonists may be mediated by NMDA receptors in 3-acetylpyridine-treated rats.

• Authors: K Kinoshita, Y Watanabe, M Yamamura, Y Matsuoka
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 343 Issue 2-3 Pg. 129-33 (Feb 19 1998) ISSN: 0014-2999 [Print] Netherlands
• PMID: 9570459 (Publication Type: Journal Article)

Chemical References

• Pyridines
• Receptors, N-Methyl-D-Aspartate
• Receptors, Thyrotropin-Releasing Hormone
• 3-acetylpyridine
• TA 0910
• Niacinamide
• Thyrotropin-Releasing Hormone

Topics

• Animals
• Cerebellar Ataxia (chemically induced, drug therapy)
• Male
• Motor Activity (drug effects)
• Niacinamide (antagonists & inhibitors)
• Pyridines (pharmacology)
• Rats
• Rats, Wistar
• Receptors, N-Methyl-D-Aspartate (drug effects, metabolism)
• Receptors, Thyrotropin-Releasing Hormone (agonists)
• Thyrotropin-Releasing Hormone (analogs & derivatives, pharmacology)