Ignavine is a naturally occurring diterpene alkaloid found in Aconiti tuber.[1][2][3][4][5] It has been reported to act as a μ-opioid receptor (MOR) positive allosteric modulator (PAM).[1][3][4][6] The drug potentiated responses to the selective MOR agonist DAMGO at low concentrations but inhibited DAMGO at high concentrations.[1][4][6] Ignavine alone has been found to produce analgesic effects in animals, but with a biphasic dose–response curve.[4][1] Although described as a MOR PAM, other research suggests that ignavine is a ligand of the orthosteric site of the MOR and does not act as a PAM.[1] Instead, it may be a MOR partial agonist.[1] However, more research is necessary to clarify its MOR actions.[1] Ignavine was first isolated by 1952[5] and its reported MOR PAM activity was first reported by 2016.[2][6]
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| Other names | 3,9,15-Trihydroxyhetisan-2-yl benzoate |
| Drug class | μ-Opioid receptor positive allosteric modulator or agonist; Analgesic |
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| Formula | C27H31NO5 |
| Molar mass | 449.547 g·mol−1 |
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See also
editReferences
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- ^ a b Remesic M, Hruby VJ, Porreca F, Lee YS (June 2017). "Recent Advances in the Realm of Allosteric Modulators for Opioid Receptors for Future Therapeutics". ACS Chem Neurosci. 8 (6): 1147–1158. doi:10.1021/acschemneuro.7b00090. PMC 5689070. PMID 28368571.
- ^ a b Kaye AD, Cornett EM, Patil SS, Gennuso SA, Colontonio MM, Latimer DR, Kaye AJ, Urman RD, Vadivelu N (June 2018). "New opioid receptor modulators and agonists". Best Pract Res Clin Anaesthesiol. 32 (2): 125–136. doi:10.1016/j.bpa.2018.06.009. PMID 30322454.
- ^ a b c d Badal S, Turfus S, Rajnarayanan R, Wilson-Clarke C, Sandiford SL (April 2018). "Analysis of natural product regulation of opioid receptors in the treatment of human disease". Pharmacol Ther. 184: 51–80. doi:10.1016/j.pharmthera.2017.10.021. PMID 29097308.
- ^ a b Saito H, Ueyama T, Naka N, Yagi J, Okamoto T (May 1982). "Pharmacological studies of ignavine, an aconitum alkaloid". Chem Pharm Bull (Tokyo). 30 (5): 1844–1850. doi:10.1248/cpb.30.1844. PMID 7116516.
- ^ a b c Ohbuchi K, Miyagi C, Suzuki Y, Mizuhara Y, Mizuno K, Omiya Y, Yamamoto M, Warabi E, Sudo Y, Yokoyama A, Miyano K, Hirokawa T, Uezono Y (August 2016). "Ignavine: a novel allosteric modulator of the μ opioid receptor". Sci Rep. 6: 31748. doi:10.1038/srep31748. PMC 4987652. PMID 27530869.