GR 82334 is a Tachykinin NK1 Receptor Antagonist

GR 82334 is a Tachykinin NK1 Receptor Antagonist

In this article, we will introduce a potent tachykinin NK1 receptor antagonist GR 82334.

GR 82334 is a Tachykinin NK1 Receptor Antagonist 2020 09 09 - GR 82334 is a Tachykinin NK1 Receptor Antagonist

GR 82334 inhibits substance P-induced sensitization by blocking SP NK1 receptors in naked mole-rats. Capsaicin application can lead to chemocnociceptive micturition reflex in rats. However, the intrathecal administration of GR 82334 at 1 but not at 0.1 nmol blocks the chemocnociceptive micturition reflex.

Additionally, GR 82334 has no effect on either micturition reflex or the urinary bladder contraction induced by perineal pinching. This result proves that specific stimuli apply in the periphery activate NK-1 receptors that contribute to urinary bladder reflex contractions. And, GR 82334 blocks this reaction.

Neuropeptides are involved in the transmission of noxious stimuli.

And the neuropeptides contains Substance P (SP) and calcitonin gene-related peptide (CGRP). Naked mole-rats naturally lack neuropeptides in cutaneous sensory neuron C-fibers. As a result, naked mole-rats display a lack of nocifensive behavior in response to certain noxious stimuli. It also does not develop thermal hyperalgesia. Furthermore, histamine does not evoke scratching in rats due to the pruritogencity is dependent upon capsaicin-sensitive C-fibers.

But in acute mechanical and thermal nociceptive tests, naked mole-rats and male C57BL/6 mice have a similar response. Although cutaneous C-fibers lack SP, the naked mole-rat spinal cord in the rat expresses a neuropeptide receptor: the neurokinin 1 receptor (NK1).

Although cutaneous C-fibers lack SP, the naked mole-rat spinal cord in the rat expresses a neuropeptide receptor: the neurokinin 1 receptor (NK1).

After intrathecal SP injection in rat, naked mole-rats exhibit nocifensive behavior in response to capsaicin and scratching in response to histamine.

GR 82334 has no effect at 10 nM in neither species, increases heat-induced foot withdrawal latency in mice at doses >100 nM, but no such increase in naked mole-rats, where doses >100 nM evoke a tendency for decreased latency.

In conclusion, as a specific reversible tachykinin NK1 receptor antagonist, GR 82334 has anti-inflammatory effects.

Reference:

[1]. A Lecci,et al. Life Sci. 1992;51(26):PL277-80.

[2]. Antje Brand, et al. PLoS One. 2010 Dec 21;5(12):e15162.

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