Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1995 Sep;40(3):223–229. doi: 10.1111/j.1365-2125.1995.tb05777.x

The cardiovascular and subjective effects of thyrotropin releasing hormone (TRH) and a stable analogue, dimethyl proline-TRH, in healthy volunteers.

N J Coupland 1, J E Bailey 1, P Glue 1, D J Nutt 1
PMCID: PMC1365101  PMID: 8527283

Abstract

1. The cardiovascular effects of TRH 0.5 mg and 1 mg and a stable TRH analogue, dimethylproline-TRH (RX77368) 1 mg, infused intravenously over 1 min were assessed in healthy volunteers in two randomised, double-blind, placebo controlled crossover studies. 2. Both doses of TRH produced significant but transient increases in blood pressure (peak delta systolic: 0.5 mg = 9.2 mm Hg, 1.0 mg = 5.2 mm Hg; peak delta diastolic: 0.5 mg = 6.4 mm Hg, 1.0 mg = 5.4 mm Hg). 3. Beat-to-beat Finapres monitoring demonstrated a rapid onset of effects of RX77368 1 mg, with significant blood pressure effects by 45-60 s from the start of the infusion (delta systolic BP: 14.2 mm Hg, delta diastolic BP: 15.8 mm Hg and delta heart rate: 8.9 mm Hg at 60 s). 4. The pressor effects of RX77368 1 mg recorded by Dinamap (peak delta systolic: 14.3 mm Hg; peak delta diastolic: 11.8 mm Hg) were sustained, with diastolic pressure still elevated (delta diastolic: 8.2 mm Hg) at 60 min. Heart rate was more transiently elevated (peak delta heart rate: 9.0 beats min-1) during the first 6 min post infusion. 5. Mild apprehension was reported for the first 6 min after RX77368 1 mg, whereas paraesthesiae were noted after TRH. Otherwise both drugs were similar in the type (flushing, nausea, acid taste, urethral sensations) and duration of subjective effects.

Full text

PDF
223

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aibiki M., Shirakawa Y., Komatsu H., Yamaguchi Y., Ogura S., Ogli K. Hypotensive and bradycardiac responses to thyrotropin-releasing hormone in a comatose patient. Clin Neuropharmacol. 1992 Jun;15(3):236–240. doi: 10.1097/00002826-199206000-00004. [DOI] [PubMed] [Google Scholar]
  2. Borowski G. D., Garofano C. D., Rose L. I., Levy R. A. Blood pressure response to thyrotropin-releasing hormone in euthyroid subjects. J Clin Endocrinol Metab. 1984 Jan;58(1):197–200. doi: 10.1210/jcem-58-1-197. [DOI] [PubMed] [Google Scholar]
  3. Carnell N. E., Feng P., Kim U. J., Wilber J. F. Preprothyrotropin-releasing hormone mRNA and TRH are present in the rat heart. Neuropeptides. 1992 Aug;22(4):209–212. doi: 10.1016/0143-4179(92)90047-z. [DOI] [PubMed] [Google Scholar]
  4. Evequoz D., Burnier M., Niederberger M., Brunner H. R., Nussberger J., Waeber B. Mechanisms of the pressor response to intravenous thyrotropin-releasing hormone in the rat. Clin Exp Pharmacol Physiol. 1994 Feb;21(2):93–100. doi: 10.1111/j.1440-1681.1994.tb02474.x. [DOI] [PubMed] [Google Scholar]
  5. Feuerstein G., Hassen A. H., Faden A. I. TRH: cardiovascular and sympathetic modulation in brain nuclei of the rat. Peptides. 1983 Sep-Oct;4(5):617–620. doi: 10.1016/0196-9781(83)90006-2. [DOI] [PubMed] [Google Scholar]
  6. Feuerstein G., Lozovsky D., Cohen L. A., Labroo V. M., Kirk K. L., Kopin I. J., Faden A. I. Differential effect of fluorinated analogs of TRH on the cardiovascular system and prolactin release. Neuropeptides. 1984 Jun;4(4):303–310. doi: 10.1016/0143-4179(84)90004-0. [DOI] [PubMed] [Google Scholar]
  7. Garbutt J. C., Mayo J. P., Little K. Y., Gillette G. M., Mason G. A., Dew B., Prange A. J., Jr Dose-response studies with protirelin. Arch Gen Psychiatry. 1994 Nov;51(11):875–883. doi: 10.1001/archpsyc.1994.03950110035006. [DOI] [PubMed] [Google Scholar]
  8. Griffiths E. C. Clinical applications of thyrotrophin-releasing hormone. Clin Sci (Lond) 1987 Nov;73(5):449–457. doi: 10.1042/cs0730449. [DOI] [PubMed] [Google Scholar]
  9. Hawley R. J., Kratz R., Goodman R. R., McCutchen C. B., Sirdofsky M., Hanson P. A. Treatment of amyotrophic lateral sclerosis with the TRH analog DN-1417. Neurology. 1987 Apr;37(4):715–717. doi: 10.1212/wnl.37.4.715. [DOI] [PubMed] [Google Scholar]
  10. Holaday J. W., Long J. B., Martinez-Arizala A., Chen H. S., Reynolds D. G., Gurll N. J. Effects of TRH in circulatory shock and central nervous system ischemia. Ann N Y Acad Sci. 1989;553:370–379. doi: 10.1111/j.1749-6632.1989.tb46658.x. [DOI] [PubMed] [Google Scholar]
  11. Horita A., Carino M. A. Centrally administered TRH produces a vasopressor response in rabbits. Proc West Pharmacol Soc. 1977;20:303–304. [PubMed] [Google Scholar]
  12. Horita A., Carino M. A. Centrally administered thyrotropin-releasing hormone (TRH) stimulates colonic transit and diarrhea production by a vagally mediated serotonergic mechanism in the rabbit. J Pharmacol Exp Ther. 1982 Aug;222(2):367–371. [PubMed] [Google Scholar]
  13. Imholz B. P., van Montfrans G. A., Settels J. J., van der Hoeven G. M., Karemaker J. M., Wieling W. Continuous non-invasive blood pressure monitoring: reliability of Finapres device during the Valsalva manoeuvre. Cardiovasc Res. 1988 Jun;22(6):390–397. doi: 10.1093/cvr/22.6.390. [DOI] [PubMed] [Google Scholar]
  14. Lampe T. H., Veith R. C., Plymate S. R., Risse S. C., Kopeikin H., Cubberley L., Raskind M. A. Pressor, norepinephrine, and pituitary responses to two TRH doses in Alzheimer's disease and normal older men. Psychoneuroendocrinology. 1989;14(4):311–320. doi: 10.1016/0306-4530(89)90033-4. [DOI] [PubMed] [Google Scholar]
  15. Manaker S., Winokur A., Rostene W. H., Rainbow T. C. Autoradiographic localization of thyrotropin-releasing hormone receptors in the rat central nervous system. J Neurosci. 1985 Jan;5(1):167–174. doi: 10.1523/JNEUROSCI.05-01-00167.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Matre V., Karlsen H. E., Wright M. S., Lundell I., Fjeldheim A. K., Gabrielsen O. S., Larhammar D., Gautvik K. M. Molecular cloning of a functional human thyrotropin-releasing hormone receptor. Biochem Biophys Res Commun. 1993 Aug 31;195(1):179–185. doi: 10.1006/bbrc.1993.2027. [DOI] [PubMed] [Google Scholar]
  17. Mellow A. M., Sunderland T., Cohen R. M., Lawlor B. A., Hill J. L., Newhouse P. A., Cohen M. R., Murphy D. L. Acute effects of high-dose thyrotropin releasing hormone infusions in Alzheimer's disease. Psychopharmacology (Berl) 1989;98(3):403–407. doi: 10.1007/BF00451695. [DOI] [PubMed] [Google Scholar]
  18. Merchenthaler I., Csernus V., Csontos C., Petrusz P., Mess B. New data on the immunocytochemical localization of thyrotropin-releasing hormone in the rat central nervous system. Am J Anat. 1988 Apr;181(4):359–376. doi: 10.1002/aja.1001810404. [DOI] [PubMed] [Google Scholar]
  19. Metcalf G., Dettmar P. W., Lynn A. G., Brewster D., Havler M. E. Thyrotropin-releasing hormone (TRH) analogues show enhanced CNS selectivity because of increased biological stability. Regul Pept. 1981 Sep;2(5):277–284. doi: 10.1016/0167-0115(81)90032-x. [DOI] [PubMed] [Google Scholar]
  20. 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 Nov;257(3):389–408. doi: 10.1016/0165-0173(82)90012-1. [DOI] [PubMed] [Google Scholar]
  21. Mitsumoto H., Salgado E. D., Negroski D., Hanson M. R., Salanga V. D., Wilber J. F., Wilbourn A. J., Breuer A. C., Leatherman J. Amyotrophic lateral sclerosis: effects of acute intravenous and chronic subcutaneous administration of thyrotropin-releasing hormone in controlled trials. Neurology. 1986 Feb;36(2):152–159. doi: 10.1212/wnl.36.2.152. [DOI] [PubMed] [Google Scholar]
  22. Modarres-Sadeghi H., Guiloff R. J. Comparative efficacy and safety of intravenous and oral administration of a TRH analogue (RX77368) in motor neuron disease. J Neurol Neurosurg Psychiatry. 1990 Nov;53(11):944–947. doi: 10.1136/jnnp.53.11.944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morley J. E. Extrahypothalamic thyrotropin releasing hormone (TRH) -- its distribution and its functions. Life Sci. 1979 Oct 29;25(18):1539–1550. doi: 10.1016/0024-3205(79)90435-1. [DOI] [PubMed] [Google Scholar]
  24. Morley J. E., Tuck M. L., Mayes D. M., Rosenblatt S., Hershman J. M. Thyrotropin-releasing hormone increases plasma norepinephrine in man. Horm Res. 1981;14(1):18–23. doi: 10.1159/000179353. [DOI] [PubMed] [Google Scholar]
  25. Pittman J. A., Jr Thyrotropin-releasing hormone. Adv Intern Med. 1974;19:303–325. [PubMed] [Google Scholar]
  26. Poulat P., Sandillon F., Marlier L., Rajaofetra N., Oliver C., Privat A. Distribution of thyrotropin-releasing hormone in the rat spinal cord with special reference to sympathetic nuclei: a light- and electron-microscopic immunocytochemical study. J Neurocytol. 1992 Mar;21(3):157–170. doi: 10.1007/BF01194975. [DOI] [PubMed] [Google Scholar]
  27. Sasek C. A., Wessendorf M. W., Helke C. J. Evidence for co-existence of thyrotropin-releasing hormone, substance P and serotonin in ventral medullary neurons that project to the intermediolateral cell column in the rat. Neuroscience. 1990;35(1):105–119. doi: 10.1016/0306-4522(90)90125-n. [DOI] [PubMed] [Google Scholar]
  28. Siren A. L., Feuerstein G., Labroo V. M., Cohen L. A., Lozovsky D. Effect of thyrotropin releasing hormone and some of its histidine analogs on the cardiovascular system and prolactin release in the conscious rat. Neuropeptides. 1986 Jul;8(1):63–70. doi: 10.1016/0143-4179(86)90066-1. [DOI] [PubMed] [Google Scholar]
  29. Sirén A. L., Lake C. R., Feuerstein G. Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat. Circ Res. 1988 Jan;62(1):139–154. doi: 10.1161/01.res.62.1.139. [DOI] [PubMed] [Google Scholar]
  30. Tsunoda S., Shiozawa Z., Mano T. Microneurographic analysis of thyrotropin-releasing hormone effects on sympathetic outflow in human muscle nerves. J Auton Nerv Syst. 1988 Sep;23(3):207–211. doi: 10.1016/0165-1838(88)90095-1. [DOI] [PubMed] [Google Scholar]
  31. Zabavnik J., Arbuthnott G., Eidne K. A. Distribution of thyrotrophin-releasing hormone receptor messenger RNA in rat pituitary and brain. Neuroscience. 1993 Apr;53(3):877–887. doi: 10.1016/0306-4522(93)90632-p. [DOI] [PubMed] [Google Scholar]
  32. Zacur H. A., Genadry R., Rock J. A., King T. M., Smith B. R., Foster G. V. Thyrotropin-releasing hormone-induced contraction of urethral and vaginal muscle. J Clin Endocrinol Metab. 1985 Oct;61(4):787–789. doi: 10.1210/jcem-61-4-787. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES