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Taltirelin Hydrate (TA-0910)

trh antinociceptive neuroprotective superagonist ataxia

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#1 Metagene

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Posted 03 August 2014 - 05:22 PM


This stuff sounds freaking awesome (in rats anyway)  I cant believe the two prior threads only generated a hand full of responses. 

 

 

Taltirelin (marketed under the tradename Ceredist) is a thyrotropin-releasing hormone (TRH) analog, which mimics the physiological actions of TRH, but with a much longer half-life and duration of effects,[1] and little development of tolerance following prolonged dosing.[2] It has nootropic,[3] neuroprotective[4] and analgesic effects.[5]

Taltirelin is primarily being researched for the treatment of spinocerebellar ataxia; limited research has also been carried out with regard to other neurodegenerative disorders, e.g., spinal muscular atrophy.[6][7][8]

 

 

 

 

 

 

TAL was studied as a treatment for neurodegenerative disorders and is the only TRH analog that has been approved for use in humans; it is used in Japan to treat patients with adult spinal muscular atrophy (Ceredist®).

 

It costs around $1000 US for a month worth of treatment if my math is right.

 

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

 

 

 

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.

 

 

Synthesis and pharmacological action of TRH analog peptide

 

 

 

The CNS stimulating actions of Taltirelin hydrate such as antagonistic actions against pentobarbital-induced anesthesia and reserpine- induced hypothermia were found to be about 100 times stronger and about 8 times longer-lasting as compared with those of TRH. Meanwhile, the affinity of Taltirelin hydrate for TRH-receptors was about 10 times lower, and the endocrine action was about 5 times less potent than those of TRH. Therefore, high CNS-selectivity and long-lasting action of Taltirelin hydrate would be attributed to its high stability in the body and low affinity for TRH-receptors. Oral administrations of Taltirelin hydrate ameliorated consiousness impairment, memory impairment and motor dysfunction in several models.

 

 

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Effects of taltirelin hydrate (TA-0910), a novel thyrotropin-releasing hormone analog, on in vivo dopamine release and turnover in rat brain.

 

 

 

Effects of taltirelin hydrate (CAS 103300-74-9, TA-0910), a novel thyrotropin-releasing hormone (TRH) analog, on the cerebral monoamine systems, especially the release and turnover of dopamine (DA) in rat brain were compared with those of TRH by intraperitoneal administration. Taltirelin hydrate (1-10 mg/kg) increased the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and corpus striatum for 3 h in a microdialysis study. TRH (30 mg/kg) also increased the levels of these substances, the potency of TRH being the same as that of taltirelin hydrate at doses of 1-3 mg/kg. Taltirelin hydrate (10 mg/kg) also caused an increase in 3-methoxytyramine (3-MT: DA metabolite) until 6 h after the treatment and L-3-dihydroxyphenylalanine (DOPA: precursor of DA and noradrenaline). Taltirelin hydrate also increased the 3-methoxy-4-hydroxyphenylglycol (MHPG: noradrenaline metabolite) level in the frontal cortex and hypothalamus, and 5-hydroxytryptophan (5-HTP: serotonin precursor) accumulation and 5-hydroxyindoleacetic acid (5-HIAA: serotonin metabolite) level in the nucleus accumbens or corpus striatum. These results suggest that taltirelin hydrate possesses not only an enhancing effect on DA release, but also a stimulating effect on the monoamine system. Moreover, these actions were 10-30 times stronger and also longer-lasting than those of TRH. In addition, the mechanisms of DA release induced by these drugs were different from those induced by methamphetamine.

 

 

Effect of TA-0910, a novel thyrotropin-releasing hormone analog, on in vivo acetylcholine release and turnover in rat brain.

 

 

 

To examine the action of a novel thyrotropin-releasing hormone (TRH) analog, TA-0910 ((-)-N-[(S)-hexahydro-1-methyl-2,6-dioxo-4-pyrimidinylcarbonyl]-L- histidyl-L-prolinamide tetrahydrate), on the cerebral cholinergic systems, the release of acetylcholine (ACh) and choline in freely-moving rats and ACh accumulation in gamma-butyrolactone (GBL, a nerve impulse flow blocker)- and physostigmine-treated rats were examined. TA-0910 (0.1-1 mg/kg, i.p.) caused a marked dose-dependent increase in extracellular ACh levels and a decrease in choline levels in the hippocampus of freely moving rats. These effects were significantly stronger and longer-lasting than similar effects of TRH. TA-0910 (1, 3 mg/kg, i.p.) depressed the ACh accumulation in the cerebral cortex and hippocampus of GBL (1000 mg/kg, i.p.)-treated rats. Moreover, this analog (1, 3 mg/kg, i.p.) increased the accumulation rate of ACh in these regions in physostigmine (1 mg/kg, i.p.)-treated rats. TRH (30 mg/kg, i.p.) affected the ACh accumulation only in the hippocampus of the GBL-treated rats. These results suggest that TA-0910 not only enhances the release of ACh, but also accelerates the ACh turnover, i.e., ACh release and synthesis, at the cholinergic neuronal terminals in normal rats.

 

http://en.wikipedia....wiki/Taltirelin

http://www.ncbi.nlm....les/PMC3466466/

http://www.ncbi.nlm..../pubmed/9503402

http://www.ncbi.nlm..../pubmed/9608876

http://www.ncbi.nlm..../pubmed/8835640


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#2 Invariant

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Posted 04 August 2014 - 12:22 AM

The effects found in these studies are almost all neurochemical instead of behavioural in nature. I am personally not able to translate a statement like "TA-0910 (0.1-1 mg/kg, i.p.) caused a marked dose-dependent increase in extracellular ACh levels and a decrease in choline levels in the hippocampus of freely moving rats." to something that is behaviorally relevant, and I somehow doubt our current understanding of the brain is sufficient for anyone to do so. For example, why do we want to increase extracellular ACh while decreasing choline levels in the hippocampus?

 

Do you know of any studies showing effects on cognitive tests, preferably in humans?


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#3 Ali Ismail

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Posted 28 April 2016 - 03:37 AM

Have you tried it ?

 



#4 sativa

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Posted 28 April 2016 - 03:37 PM

Thyrotropin-releasing hormone (TRH), also called thyrotropin-releasing factor (TRF) or thyroliberin, is a releasing hormone, produced by the hypothalamus, that stimulates the release of thyrotropin (thyroid-stimulating hormone or TSH) and prolactin from the anterior pituitary.


Wouldn't the release of thyroid-stimulating hormone (TSH) and prolactin potentially have undesirable consequences in terms of disregulating homeostasis?
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#5 PeopleProgrammer

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Posted 02 July 2016 - 02:11 AM

Found a source, it is sold as ceredist in japan. 28 tablets cost $775.18 (which is absolutely outrageous, imho) and here is a link https://www.mimaki-f...eredist&x=0&y=0 I couldnt find it anywhere else. perhaps a group buy is in order?

 

Thyrotropin releasing hormone, which taltirelin is an analog of, is at the top of the endocrine signalling cascade. it is released from the hypothalamus, and it stimulates release of thyroid stimulating hormone from the anterior pituitary. then the thyroid is stimulated by TSH to release thyroxine. since there is no upstream signalling relative to TRH, the only downregulation that can occur to ameliorate abnormally high TRH levels is to  either reduce endogenous synthesis of TRH or reduce the number of TRH receptors (which does not appear to happen, hence the lack of tolerance build up). the release of TRH itself is neurological in nature. the release of prolactin is the only aspect of this which strikes me as potentially problematic. however there are ways to counteract and reduce prolactin, so I wouldn't call it a deal breaker. for the most part, homeostasis should not be able to fight the effects of the drug.



#6 dwaaam

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Posted 02 July 2016 - 08:34 AM

Found a source, it is sold as ceredist in japan. 28 tablets cost $775.18 (which is absolutely outrageous, imho) and here is a link https://www.mimaki-f...eredist&x=0&y=0 I couldnt find it anywhere else. perhaps a group buy is in order?

 

Thyrotropin releasing hormone, which taltirelin is an analog of, is at the top of the endocrine signalling cascade. it is released from the hypothalamus, and it stimulates release of thyroid stimulating hormone from the anterior pituitary. then the thyroid is stimulated by TSH to release thyroxine. since there is no upstream signalling relative to TRH, the only downregulation that can occur to ameliorate abnormally high TRH levels is to  either reduce endogenous synthesis of TRH or reduce the number of TRH receptors (which does not appear to happen, hence the lack of tolerance build up). the release of TRH itself is neurological in nature. the release of prolactin is the only aspect of this which strikes me as potentially problematic. however there are ways to counteract and reduce prolactin, so I wouldn't call it a deal breaker. for the most part, homeostasis should not be able to fight the effects of the drug.

 

True Life Research also has some in stock, although also at outrages price but somewhat lower than the japanese source, $1.9/mg compared to $5.5/mg. Their business practices seem somewhat dubious, their homemade formulas was found to be mostly very expensive taurine.
https://teamtlr.com/...tirelin-98.html


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#7 Carl Leninger

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Posted 19 May 2017 - 01:21 AM

Suaway.... also carries it!

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#8 beatstar

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Posted 05 February 2020 - 11:27 PM

it should work better than thyrotrophin. I bought it from suaway.com







Also tagged with one or more of these keywords: trh, antinociceptive, neuroprotective, superagonist, ataxia

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