• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.211-214
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• 1997

In the present study, we investigated the mechanisms of antinociceptive effect and thermoregulatory action of capsaicin in guinea pigs. The administration of capsaicin (5 mg/kg, s.c.) caused a significant decrease in frequency of eye wiping, an indicative of nociceptive threshold. This antinociceptive effect of calsaicin was abolished by co-administration of capsazepine (30 mg/kg, s.c.) with capsaicin, suggesting the involvement of a vanilloid receptor in the antinociceptive action of capsaicin. The administration of capsaicin (1 mg/kg, s.c.) produced a significant decrease in body temperature of guinea pigs. The maximum decrease in body temperature by 2 degrees was shown 1 hour after the treatment, and this decrease was not reversed by coadministration of capsazepine. In conclusion, it is suggested that the mechanism of action of capsaicin-induced thermoregulation involves different pathways from that of capsaicin-induced antinociception.

• Journal of Food Hygiene and Safety
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• v.9 no.3
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• pp.163-168
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• 1994

In the present study we investigated the peripheral function of capsaicin and KR-25018, a newly synthesized capsaicin derivative, which was demonstrated to have a potent analgesic activity through different mechanism from morphine and nonsteroidal antiinflammatory drugs. Capsaicin (10-8~10-5 M) and KR-25018 (10-8~10-5 M) produced concentration-dependent contractions of the isolated guinea pig bronchi. There were no significant differences in the maximum response and the EC50 values (EC50: 0.137$\pm$0.025 $\mu$M and 0.097$\pm$0.031 $\mu$M for capsaicin and KR-25018, respectively, P>0.05). Phosphoramidon (10 $\mu$M) and indomethacin (10 $\mu$M) had no significant effect on contractile response to the submaximal concentration range of capsaicin and KR-25018 (3$\times$10-9~3$\times$10-7 M). The response to KR-25018, like that to capsaicin, was significantly inhibited by ruthenium red with reduction in the maximum response, which is indicative of non-competitive antagonism. A further common feature of the responses to capsaicin and KR-25018 in the guinea pig bronchi was their sensitivity to capsazepine. Capsazepine caused a rightward parallel shift in concentration-response curves obtained by capsaicin and KR-25018. the pA2 values of capsazepine were 5.90 and 5.99 against capsaicin and KR-25018 response, respectively. In conclusion, KR-25018 and capsaicin exert their contractile effects in the isolated guinea pig bronchial muscle by common mechanisms, probably via the activation of a specific receptor.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.253-253
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• 1996

KR-25018 과 capsaicin 모두 용량의존적으로 진통효과를 나타내었으며 효력은 KR-25018이 capsaicin 보다 약간 강하거나 비슷하였고, 두 약물 모두 10 mg/kg에서 최대 효과를 나타내었다. KR-25018 과 capsaicin의 투여 농도에 의존적으로 기관지의 substance P 양이 감소하였으며 두 약물 모두 5 mg/kg에서 최대효과를 나타내었다. Capsaicin 1 mg/kg 전처치에 의해 기니픽의 체온이 30 분부터 감소하였으나, KR-25018 1 mg/kg에 의해서는 체온변화가 훨씬 미약하였다. Capsazepine 의 병용투여에 의해 두 약물의 진통작용 및 substance P 감소작용은 모두 억제되었으나 체온 변화에 대해서는 capsazepine이 아무런 영향을 미치지 않았다.

• YAKHAK HOEJI
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• v.43 no.1
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• pp.55-60
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• 1999

To investigate analgesic mechanism of capsaicin and its analogues (capaicinoids) adenosine release was measured by high performance liquid chromatography from rat spinal cord synaptosomes. Exposure of synaptosomes to $K^+$ and morphine produced a dose dependent release of adenosine in the presence of $Ca^{++}$. Capsaicin (0.1, 1, $10{\;}{\mu}M$), and its analogues: NE-19550 (1, 10, $100{\;}{\mu}M$), DMNE (1, 10, $100{\;}{\mu}M$) and KR 25018 (0.1, 1, $10{\;}{\mu}M$) produced a concentration dependent release of adenosine in the presence of $Ca^{++}$. Nifedifine, L-type voltage sensitive calcium channel blocker, inhibited $K^+$ (6, 12 mM)-and morphine ($10{\;}{\mu}M$)-evoked release of adenosine partially. Capsazepine, a novel capsaicin selective antagonist, blocked only capsaicin and capsaicinoids induced release of adenoside. Therefore, it is suggested that the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involves actvation of capsaicin specific receptor and capsaicin sensitive $Ca^{++}$. channel.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.350.1-350.1
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• 2002

A series of diaralkylthiourea derivatives was prepared and tested for its antagonistic activity against vanilloid receptor. In this study we explored the possibility of selected compound type (Ⅰ) with tetrahydronaphthyl group as rigid pendant moiety. Our premise for antagonistic activity of molecules was modeled on the capsazepine. the first antagonist for vanilloid receptor. These compounds (Ⅰ) showed less potent antagonistic activity than that of capsazepine. but they were devoid of agonistic activity. (omitted)

• YAKHAK HOEJI
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• v.44 no.6
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• pp.499-504
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• 2000

We previously demonstrated that 6-paradol, a compound structurally related to capsaicin, showed to produce prolonged analgesia in experimental animals. The effects of 6-paradol on the release of adenosine were investigated in the rat spinal cord synaptosomes by high performance liquid chromatography. In the presence of $Ca^{++}$, adenosine was released from synaptosomes of rat spinal cord by 6-paradol and capsaicin in a dose dependent manner. Nifedifine, L-type voltage sensitive calcium channel blocker, was found to be ineffective in releasing adenosine by $10\;{\mu}M$ 6-paradol. After exposure to $10\;{\mu}M$ capsazepine, a novel capsaicin selective antagonist, the level of adenosine evoked by $10\;{\mu}M$ 6-paradol was decreased by 75%, and that evoked by $10\;{\mu}M$ capsaicin was blocked completely. These results suggest that the analgesic effect of 6-paradol might be mediated by the vanilloid (capsaicin) sensitive pathway, or the direct binding to the vanilloid receptor.

• Restorative Dentistry and Endodontics
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• v.20 no.2
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• pp.423-431
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• 1995

Trigeminal spinal sensory nucleus is a main relay site in transmission of orofacial pain. Glutamate and aspartate playa role in transmission of primary afferents. This experiment was performed to study the role of capsaicin, KR-25018 and shogaol on the release of glutamate and aspartate from trigeminal spinal sensory nucleus. Release of excitatory amino acids(EAAs) was induced by electrical stimulation of oral mucosa with innocuous or noxious stimuli. Capsaicin($10{\mu}M$), KR-25018($10{\mu}M$), shogaol($10{\mu}M$), ruthenium red and capsazapine were added to perfusion solution to observe the changes in EAA release, and glutamate and aspartate were determined by HPLC. Release of glutamate and aspartate from trigeminal sensory nucleus was increased by noxious stimulation of oral mucosa, but innocuous stimulation did not affect on the release of EAA Capsaicin and KR-25018 increased the release of glutamate and aspartate, and effect of KR-25018 on release of EAA was more potent than capsaicin. But shogaol had a weak effect on release of EAA. Effect of capsaicin and KR-25018 was partially blocked by capsaicin antagonists, ruthenium red and capsazepine.

• Restorative Dentistry and Endodontics
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• v.25 no.3
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• pp.407-420
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• 2000

삼차신경절의 뉴런이 구강악안면영역에서의 촉각, 입각, 온도각 및 통각 등 다양한 감각을 중추신경계로 전달하는 역할을 하는 것은 주지의 사실이다. 이러한 신경전달에 있어서 이온통로는 감각정보를 전달하는데 핵심적인 역할을 수행하며 특히 소디움 통로는 활동전위의 발생에 중요하다. 소디움 통로는 tetrodotoxin-sensitive(TTX-s) 및 tetrodotoxin-resistant(TTX-r) 통로로 나누어지는 데 이 중 TTX-r 통로에 발생되는 tetrodotoxin-resistant sodium current(TTX-r $I_{Na}$)는 capsaicin에 민감한 일차구심신경세포에서 유해자극에 의해 통각신호를 발생시키고 전달하는데 중요하다. 또한 칼슘 통로는 시냅스 전도에 있어서 필수적인 역할을 수행하고 있다 한편 치과영역에서 치수의 진정 목적으로 eugenol이 흔히 사용되고 있다. 그러나 eugenol의 그 작용 기전에 대해서 현재까지 이온 통로에 대한 상세한 결과가 없는 실정이며 최근의 보고에 의하면 eugenol이 capsaicin 수용기를 통하여 감각신경에 대한 억제작용을 나타낸다고 한다. 따라서 본 실험은 eugenol과 capsaicin이 흰쥐의 삼차신경절의 TTX-r $I_{Na}$와 칼슘통로에 어떠한 영향을 미치는지를 알아보고 eugenol이 capsaicin 수용기를 통하여 작용하는지를 검증하고자 시행되었다. 삼차신경절 뉴런은 100~150g의 흰쥐의 삼차신경절로부터 외과적으로 절제하여 통법의 화학적 및 기계적 처리를 통해 단일세포로 분리하였고 이를 whole-cell patch clamp 방법을 이용하여 시행한 바 다음과 같은 결론을 얻었다. 1. 1mM의 dugenol은 흰쥐 삼차신경절 뉴런의 TTX-r $I_{Na}$와 HVA $I_{Ca}$를 억제하였다. 2. $1{\mu}m$의 capsaicin은 흰쥐 삼차신경절 뉴런의 TTX-r $I_{Na}$와 HVA $I_{Ca}$를 억제하였다. 3. Capsazepine은 capsaicin의 HVA $I_{Ca}$에 대한 억제작용을 차단하였다. 4. Capsazepine은 capsaicin의 HVA $I_{Ca}$에 대한 억제작용을 차단하지 못하였다. 결론적으로 eugenol과 capsaicin은 tetrodotoxin-resistant sodium current(TTX-r $I_{Na}$)와 high voltage-activated calcium current(HVA $I_{Ca}$)를 모두 억제하는 것으로 나타났으며, 이러한 작용이 통각의 발생과 시냅스 전달과정을 차단하여 치수 진정 목적으로 많이 사용하는 eugenol의 작용기전으로 판단된다. 한편 capsaicin의 길항제인 capsazepine을 전처치하였을 때에도 eugenol의 HVA $I_{Ca}$에 대한 억제효과는 변화가 없었다. 이와같은 결과로 보아 HVA $I_{Ca}$에 관한 한 eugenol은 capsaicin 수용기를 통하여 나타나지 않는 것으로 사료된다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.294-294
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• 1994

To investigate analgesic mechanism of capsaicin and its analogues (capsaicinoids), release of adenosine was measured by high performance liquid chromatography from dorsal spinal cord synaptosomes, Exposure of synaptosomes to K$\^$+/ and morphine produced a dose dependent release of adenosine in the presence of Ca$\^$++/. Capsaicin (0.1, 1, 10 M), and its analogues 6-paradol (1, 10 M), NE-19550 (1, 10, 100 M), DMNE (1, 10, 100 M) and KR 25018 (0.1, 1, 10 M) produced a dose dependent release of adenosine in the presence of Ca$\^$++/. Nifedipine, L-type voltage sensitive calcium channel blocker, inhibited K$\^$+/ (6, 12 mM)- and morphine (10 M)-evoked release of adenosine completely, but inhibited capsaicin, and capsaicinoids-evoked release of adenosine partially. Capsazepine, a novel capsaicin select ive antagonist, blocked only capsaicin and capsaicinoids induced release of adenosine. Therefore, the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involve activation of capsaicin specific receptor and capsaicin sensitive Ca$\^$++/ channel.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.244.1-244.1
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• 2003

Advances in understanding of pain and analgesia have been made. Over the past few years, we have designed and synthesized a series of VR agonists, based on the structures of 12-HPETE and capsaicin. the natural VR agonist. But for the development of analgesic drugs, these synthetic VR agonists had problems like burning sensation. hypothermia. etc. So our recent studoes have focused on designs and syntheses of VR antagonists based on the structure of capsaicin(natural VR agonist), and capsazepine(synthetic VR antagonist). (omitted)