Effects of a New TRH Analogue, YM-14673 on the Central Nervous System

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1987 Nov 1

PMID 3125485

Citations 7

Authors

M Yamamoto

M Shimizu

Affiliations

Soon will be listed here.

Abstract

The effects of a new TRH analogue, YM-14673 (N alpha-[[S)-4-oxo-2-azetidinyl)carbonyl]-L-histidyl-L-prolinamide dihydrate) on the central nervous system were compared with those of TRH. YM-14673 was 10-40 times more potent than TRH in antagonizing pentobarbital-induced sleep and hypothermia, and ethanol-induced hypothermia in mice. YM-14673 accelerated recovery from disturbed consciousness induced by concussive head trauma in mice and normalized the behavior and spontaneous EEG disturbed by electrolytic lesion of the hypothalamus in cats with 25-100 times greater potency than that of TRH. In the tests on pentobarbital sleeping time and EEG disturbance, the cerebral activating activity of YM-14673 was 8-36 times longer-lasting than that of TRH. These results indicate that YM-14673 possesses potent arousal effects on the central nervous system. The mode of action of YM-14673 was also discussed.

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References

Sobue I, Yamamoto H, Konagaya M, Iida M, Takayanagi T . Effect of thyrotropin-releasing hormone on ataxia of spinocerebellar degeneration. Lancet. 1980; 1(8165):418-9. DOI: 10.1016/s0140-6736(80)90963-0. View

Yamamoto M, Shimizu M . Cerebral activating properties of indeloxazine hydrochloride. Neuropharmacology. 1987; 26(7A):761-70. DOI: 10.1016/0028-3908(87)90239-5. View

Brewster D, Dettmar P, Metcalf G . Biologically stable analogues of TRH with increased neuropharmacological potency. Neuropharmacology. 1981; 20(5):497-503. DOI: 10.1016/0028-3908(81)90184-2. View

Engel W, Siddique T, Nicoloff J . Effect on weakness and spasticity in amyotrophic lateral sclerosis of thyrotropin-releasing hormone. Lancet. 1983; 2(8341):73-5. DOI: 10.1016/s0140-6736(83)90060-0. View

Faden A, JACOBS T, Smith G, Green B, Zivin J . Neuropeptides in spinal cord injury: comparative experimental models. Peptides. 1983; 4(5):631-4. DOI: 10.1016/0196-9781(83)90009-8. View

Metcalf G, Dettmar P, Lynn A, Brewster D, Havler M . Thyrotropin-releasing hormone (TRH) analogues show enhanced CNS selectivity because of increased biological stability. Regul Pept. 1981; 2(5):277-84. DOI: 10.1016/0167-0115(81)90032-x. View

Metcalf G . Regulatory peptides as a source of new drugs--the clinical prospects for analogues of TRH which are resistant to metabolic degradation. Brain Res. 1982; 257(3):389-408. DOI: 10.1016/0165-0173(82)90012-1. View

HOLLANDER C, Mitsuma T, Shenkman L, Woolf P, Gershengorn M . Thyrotropin-releasing hormone: evidence for thyroid response to intravenous injection in man. Science. 1972; 175(4018):209-10. DOI: 10.1126/science.175.4018.209. View

Yarbrough G . On the neuropharmacology of thyrotropin releasing hormone (TRH). Prog Neurobiol. 1979; 12(3-4):291-312. DOI: 10.1016/0301-0082(79)90012-1. View

10.

Prange Jr A, Lara P, Wilson I, ALLTOP L, Breese G . Effects of thyrotropin-releasing hormone in depression. Lancet. 1972; 2(7785):999-1002. DOI: 10.1016/s0140-6736(72)92407-5. View

11.

Cott J, Breese G, Cooper B, Barlow S, Prange Jr A . Investigations into the mechanism of reduction of ethanol sleep by thyrotropin-releasing hormone (TRH). J Pharmacol Exp Ther. 1976; 196(3):594-604. PMC: 2913895. View

12.

Huger F, Patrick G . Effect of concussive head injury on central catecholamine levels and synthesis rates in rat brain regions. J Neurochem. 1979; 33(1):89-95. DOI: 10.1111/j.1471-4159.1979.tb11710.x. View

13.

Yokohama S, Yamashita K, Toguchi H, Takeuchi J, Kitamori N . Absorption of thyrotropin-releasing hormone after oral administration of TRH tartrate monohydrate in the rat, dog and human. J Pharmacobiodyn. 1984; 7(2):101-11. DOI: 10.1248/bpb1978.7.101. View

14.

INANAGA K, Inoue Y . Effect of a thyrotropin releasing hormone analog in a patient with myoclonus epilepsy. Kurume Med J. 1981; 28(3):201-10. DOI: 10.2739/kurumemedj.28.201. View

15.

Miyamoto M, Fukuda N, Narumi S, Nagai Y, Saji Y, Nagawa Y . Gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide citrate (DN-1417): a novel TRH analog with potent effects on the central nervous system. Life Sci. 1981; 28(8):861-9. DOI: 10.1016/0024-3205(81)90047-3. View

16.

Plotnikoff N, Prange Jr A, Breese G, Wilson I . Thyrotropin releasing hormone: enhancement of DOPA activity in thyroidectomized rats. Life Sci. 1974; 14(7):1271-8. DOI: 10.1016/0024-3205(74)90435-4. View

17.

Jacobs L, Snyder P, Wilber J, UTIGER R, Daughaday W . Increased serum prolactin after administration of synthetic thyrotropin releasing hormone (TRH) in man. J Clin Endocrinol Metab. 1971; 33(6):996-8. DOI: 10.1210/jcem-33-6-996. View

18.

Marshall L, Bruce D, Bruno L, Langfitt T . Vertebrobasilar spasm: a significant cause of neurological deficit in head injury. J Neurosurg. 1978; 48(4):560-4. DOI: 10.3171/jns.1978.48.4.0560. View