Effect on Weakness and Spasticity in Amyotrophic Lateral Sclerosis of Thyrotropin-Releasing Hormone

Engel, W. King; Siddique, Teepu; Nicoloff, JohnT.

doi:10.1016/s0140-6736(83)90060-0

Cited by 197 publications

(32 citation statements)

References 17 publications

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“…This may be due partly to the different routes of TRH administration and partly to the various doses used. However, studies of the TRH kinetics and its chronic effects on the endo crine system are of major clinical impor tance as can be seen by the recent applica tion of TRH and TRH analogues in the treatment of some neurologic diseases [9,10],…”

Section: Introductionmentioning

confidence: 99%

Aspects of Chronic Oral Treatment with Thyrotropin-Releasing Hormone: The Hypothalamic-Pituitary-Thyroid Axis in Rats

Duntas

Astier

et al. 1991

Pharmacology

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The effects of 16 days of oral treatment with thyrotropin-releasing hormone (TRH, 1 mg/24 h) on serum levels of thyrotropin (TSH), thyroxine (T₄) and triiodothyronine (T3) and the kinetics of TRH in the blood were studied in normal rats. A second group of animals served as controls. TRH was dissolved by sonification (10 mg/l) and was stable in tap water. TRH was measured by a radioimmunoassay procedure (normal range: 20–80 pmol/l, antiserum K2B9 1:120,000 final dilution). An increase in basal TSH (7,200 ± 440 ng/l, mean ± SD) was found after 2 days of treatment (11,420 ± 810 ng/l), but a significant increase was observed after 5 days of treatment (12,530 ± 640 ng/l, p < 0.001). T₄ serum concentrations remained in the normal range during the entire period of study, whereas T₃serum concentrations (0.76 ± 0.1 µg/l) were increased to 1.22 ± 0.2 µg/l on day 5 (p < 0.001). A subsequent decline of TSH, T₄ and T₃ up to the end of the study was observed. TRH_max concentrations were registered on day 5 (790 ± 24 pmol/l). The mean value of TRH_max was 723 ± 34 pmol/l. To improve the stability of TRH in tap water, 1-ml samples of drinking water with dissolved TRH were measured. The mean TRH concentration in drinking water was 73 ± 1.5% (SD). No significant correlations were found between the area under the curve of TSH (184,340 ng·l^–1·24 h) and that of TRH (14,954 pmol·l^–1·24 h). These findings suggest that (1) chronic treatment with oral TRH cannot induce hyperthyroidism in rats, (2) oral TRH is absorbed when dissolved in tap water where it is stable and (3) the enzymatic process of TRH degradation is saturated at high doses of the peptide used in this study. Chronic treatment with oral TRH is a useful model to study the pituitary reserves in relation to TRH blood levels.

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Section: Introductionmentioning

confidence: 99%

Aspects of Chronic Oral Treatment with Thyrotropin-Releasing Hormone: The Hypothalamic-Pituitary-Thyroid Axis in Rats

Duntas

Astier

et al. 1991

Pharmacology

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“…It exhibits a broad spectrum of stimulatory effects (Griffiths, 1987) which are probably mediated via receptors very similar to those moderating the endocrine function of the peptide in the pituitary gland (Burt & Taylor, 1980;Dettmar et al, 1983a,b;. TRH has been found capable of preventing neuronal damage (Freedman et al, 1986;, promoting recovery following spinal trauma (Faden et al, 1981) and relieving weakness and spasticity in motor neurone disease (MND) (Engel et al, 1983). However, its clinical potential in these areas has not been realised, possibly a consequence of the peptide's short biological half life due to its rapid metabolism by pyroglutamyl aminopeptidases and deamidase enzymes in body tissues and fluids (Bassiri & Utiger, 1981;Coggins et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological and biochemical comparison of thyrotropin releasing hormone (TRH) and di‐methyl proline‐TRH on pituitary GH₃ cells

McDermott

Wilkin

Dickinson

1990

British J Pharmacology

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“…TRH stimulates cholinergic and monoaminergic turnover, depolarizes spinal motoneurons, enhances CNS arousal, modulates locomotor activity, regulates respiration, and modulates pain perception and epileptic threshold (for review, see Jackson, 1982;Metcalf, 1982;Sharif, 1985;Griffiths and Bennett, 1987;Winokur et al, 1989). Furthermore, TRH has been shown to have beneficial effects in depression (Prange et al, 1972), brain and spinal injuries (Faden, 1986), spinocerebellar degeneration (Sobue et al, 1983), and motoneuron diseases (Engel et al, 1983). Therapeutic indications of TRH for these diseases are, however, still very limited partially because of the pharmacokinetic profile of TRH.…”

Section: Abstract: Thyrotropin-releasing Hormone; Narcolepsy; Cataplmentioning

confidence: 99%

Effects of Thyrotropin-Releasing Hormone and Its Analogs on Daytime Sleepiness and Cataplexy in Canine Narcolepsy

et al. 1997

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The therapeutic potential of thyrotropin-releasing hormone (TRH) and TRH analogs in narcolepsy, a sleep disorder characterized by abnormal rapid eye movement (REM) sleep and daytime sleepiness, was examined using the canine model. The effects of TRH and the biologically stable TRH analogs CG3703, CG3509, and TA0910 on daytime sleep and cataplexy, a symptom of abnormal REM sleep, were assessed using polysomnographic recordings and the food elicited cataplexy test (FECT), respectively. CG3703 (100 and 400 g/kg, i.v.) and TA0910 (100 and 400 g/kg, i.v.) significantly increased wakefulness and decreased sleep in narcoleptic canines, whereas TRH (400 and 1600 g/kg, i.v.) had no significant effect. TRH (25-1600 g/kg, i.v.) and all three TRH analogs, CG3703 (6.25-400 g/kg, i.v., and 0.25-16 mg/kg, p.o.), CG3509 (25-1600 g/kg, i.v.), and TA0910 (25-1600 g/kg, i.v.), significantly reduced cataplexy in canine narcolepsy. These compounds did not produce any significant side effects during behavioral assays, nor did they alter free T 3 and T 4 levels in serum even when used at doses that completely suppressed cataplexy. Although more work is needed to establish the mode of action of TRH analogs on alertness and REM sleep-related symptoms, our results suggest a possible therapeutic application for TRH analogs in human sleep disorders.

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Effect on Weakness and Spasticity in Amyotrophic Lateral Sclerosis of Thyrotropin-Releasing Hormone

Cited by 197 publications

References 17 publications

Aspects of Chronic Oral Treatment with Thyrotropin-Releasing Hormone: The Hypothalamic-Pituitary-Thyroid Axis in Rats

Aspects of Chronic Oral Treatment with Thyrotropin-Releasing Hormone: The Hypothalamic-Pituitary-Thyroid Axis in Rats

Pharmacological and biochemical comparison of thyrotropin releasing hormone (TRH) and di‐methyl proline‐TRH on pituitary GH₃ cells

Effects of Thyrotropin-Releasing Hormone and Its Analogs on Daytime Sleepiness and Cataplexy in Canine Narcolepsy

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Effect on Weakness and Spasticity in Amyotrophic Lateral Sclerosis of Thyrotropin-Releasing Hormone

Cited by 197 publications

References 17 publications

Aspects of Chronic Oral Treatment with Thyrotropin-Releasing Hormone: The Hypothalamic-Pituitary-Thyroid Axis in Rats

Aspects of Chronic Oral Treatment with Thyrotropin-Releasing Hormone: The Hypothalamic-Pituitary-Thyroid Axis in Rats

Pharmacological and biochemical comparison of thyrotropin releasing hormone (TRH) and di‐methyl proline‐TRH on pituitary GH3 cells

Effects of Thyrotropin-Releasing Hormone and Its Analogs on Daytime Sleepiness and Cataplexy in Canine Narcolepsy

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Pharmacological and biochemical comparison of thyrotropin releasing hormone (TRH) and di‐methyl proline‐TRH on pituitary GH₃ cells