Miltirone
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| Other names | Rosmariquinone |
| Routes of administration | Oral[1] |
| Drug class | GABAA receptor positive allosteric modulator; Anxiolytic |
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| Chemical and physical data | |
| Formula | C19H22O2 |
| Molar mass | 282.383 g·mol−1 |
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Miltirone, also known as rosmariquinone, is an alkaloid found in plants such as Salvia rosmarinus (rosemary) and Salvia miltiorrhiza (danshen, red sage, or Chinese sage).[2][1][3] It is a diterpene quinone, a group of compounds that are also known as tanshinones.[1]
Pharmacology
The drug is a nonbenzodiazepine GABAA receptor positive allosteric modulator, binding to the benzodiazepine allosteric site of the receptor complex with a relatively low affinity (IC50) of 300 nM and acting as a partial agonist.[2][1][4] It was orally active in animals and produced anxiolytic-like effects, but in contrast to diazepam, did not produce acute muscle relaxant effects and did not cause dependence or withdrawal with chronic administration.[5][2][1] As a tanshinone, miltirone is structurally distinct from other known benzodiazepine receptor ligands.[1]
Development
Miltirone was first described in the scientific literature by 1970.[6] It was isolated and described in red sage by 1970[6][1] and in rosemary by 1985.[3] The GABAA receptor potentiation of miltirone was described in 1991.[1] The drug was under formal pharmaceutical development by Abbott Laboratories for the treatment of anxiety disorders, but development was discontinued.[7]
Synthetic analogues of miltirone with greater potency as GABAA receptor positive allosteric modulators (e.g., affinity (IC50 = 50 nM or improved by 6-fold) have been developed and reported.[5][8]
See also
References
- ^ a b c d e f g h Lee CM, Wong HN, Chui KY, Choang TF, Hon PM, Chang HM (June 1991). "Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza". Neuroscience Letters. 127 (2): 237–241. doi:10.1016/0304-3940(91)90802-z. PMID 1652718.
- ^ a b c Nilsson J, Sterner O (October 2011). "Modulation of GABA(A) receptors by natural products and the development of novel synthetic ligands for the benzodiazepine binding site". Current Drug Targets. 12 (11): 1674–1688. doi:10.2174/138945011798109509. PMID 21561420.
- ^ a b Houlihan CM, Ho C, Chang SS (1985). "The structure of rosmariquinone — A new antioxidant isolated from Rosmarinus officinalis L.". Journal of the American Oil Chemists' Society. 62 (1): 96–98. doi:10.1007/BF02541500. ISSN 0003-021X. Retrieved 1 October 2025.
- ^ Mostallino MC, Mascia MP, Pisu MG, Busonero F, Talani G, Biggio G (June 2004). "Inhibition by miltirone of up-regulation of GABAA receptor alpha4 subunit mRNA by ethanol withdrawal in hippocampal neurons". European Journal of Pharmacology. 494 (2–3): 83–90. doi:10.1016/j.ejphar.2004.04.021. PMID 15212961.
- ^ a b Johnston GA (2005). "GABA(A) receptor channel pharmacology". Current Pharmaceutical Design. 11 (15): 1867–1885. doi:10.2174/1381612054021024. PMID 15974965.
- ^ a b Hayashi T, Kakisawa H, Hsu HY, Chen YP (1970). "The structure of miltirone, a new diterpenoid quinone". Journal of the Chemical Society D: Chemical Communications (5): 299a. doi:10.1039/c2970000299a. ISSN 0577-6171. Retrieved 1 October 2025.
- ^ "Miltirone". AdisInsight. 1 February 2013. Retrieved 1 October 2025.
- ^ Chang HM, Chui KY, Tan FW, Yang Y, Zhong ZP, Lee CM, et al. (May 1991). "Structure-activity relationship of miltirone, an active central benzodiazepine receptor ligand isolated from Salvia miltiorrhiza Bunge (Danshen)". Journal of Medicinal Chemistry. 34 (5): 1675–1692. doi:10.1021/jm00109a022. PMID 1851844.