Lack of behavioral tolerance by repeated treatment with taltirelin hydrate, a thyrotropin-releasing hormone analog, in rats

Asai, Hidetoshi; Asahi, Toru; Yamamura, Masatoshi; Yamauchi-Kohno, Rikako; Saito, Akira

doi:10.1016/j.pbb.2005.11.004

Cited by 10 publications

(13 citation statements)

References 28 publications

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“…As depression may accompany fatigue in cancer patients [40, 41] and a previous study reports that a mouse model of chronic social stress-induced depression increases fatigue-like behavior in their treadmill testing protocol [42], a drug like TAL may be a particularly desirable therapy, potentially alleviating both depression and fatigue. Moreover, repeated TAL administration consistently reduced fatigue-like behavior in healthy mice and previous studies found no behavioral tolerance for its other effects (e.g., increasing motor activity in rats [43] or reducing ataxia in mice [44]). As such, we anticipate that, if initially effective, TAL would remain efficacious with prolonged treatment in humans.…”

Section: Discussionmentioning

confidence: 80%

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue

Dougherty

Wolff

Cullen

et al. 2017

Pharmacological Research

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Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans.

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Section: Discussionmentioning

confidence: 80%

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue

Dougherty

Wolff

Cullen

et al. 2017

Pharmacological Research

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“…In addition, taltirelin, a synthetic thyrotropin-releasing hormone (TRH) analog, effectively improves sports activity. 120 Cocaine, which causes a rapid sympathetic response, significantly increases endurance during high-intensity exercise. 121 Modafinil, a new drug type that acts on the central nervous system and keeps subjects awake, 122 markedly prolongs exercise time to exhaustion 123 and has been widely used in the war to allow people to resist fatigue.…”

Section: Potential Treatment For Muscle Fatiguementioning

confidence: 99%

Muscle fatigue: general understanding and treatment

et al. 2017

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Muscle fatigue is a common complaint in clinical practice. In humans, muscle fatigue can be defined as exercise-induced decrease in the ability to produce force. Here, to provide a general understanding and describe potential therapies for muscle fatigue, we summarize studies on muscle fatigue, including topics such as the sequence of events observed during force production, in vivo fatigue-site evaluation techniques, diagnostic markers and non-specific but effective treatments.

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“…In humans, by contrast, only a single type of receptor for TRH, TRH-R, is expressed that is more similar to TRH-R1 than TRH-R2 (Duthie et al, 1993; Matre et al, 1993). It has been reported that TAL binds with lower affinity than TRH to receptors in rat or mouse pituitary and in brain tissue preparations (Kinoshita et al, 1997; Asai et al, 1999, 2005). However, the pharmacology of TAL at TRH-R has not been characterized.…”

Section: Introductionmentioning

confidence: 99%

Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor

2012

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Taltirelin (TAL) is a thyrotropin-releasing hormone (TRH) analog that is approved for use in humans in Japan. In this study, we characterized TAL binding to and signaling by the human TRH receptor (TRH-R) in a model cell system. We found that TAL exhibited lower binding affinities than TRH and lower signaling potency via the inositol-1,4,5-trisphosphate/calcium pathway than TRH. However, TAL exhibited higher intrinsic efficacy than TRH in stimulating inositol-1,4,5-trisphosphate second messenger generation. This is the first study that elucidates the pharmacology of TAL at TRH-R and shows that TAL is a superagonist at TRH-R. We suggest the superagonism exhibited by TAL may in part explain its higher activity in mediating central nervous system effects in humans compared to TRH.

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Lack of behavioral tolerance by repeated treatment with taltirelin hydrate, a thyrotropin-releasing hormone analog, in rats

Cited by 10 publications

References 28 publications

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue

Muscle fatigue: general understanding and treatment

Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor

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