Chemistry:Miltirone
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).[1][2][3] It is a diterpene quinone, a group of compounds that are also known as tanshinones.[2]
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.[1][2][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][1][2] As a tanshinone, miltirone is structurally distinct from other known benzodiazepine receptor ligands.[2]
Development
Miltirone was first described in the scientific literature by 1970.[6] It was isolated and described in red sage by 1970[6][2] and in rosemary by 1985.[3] The GABAA receptor potentiation of miltirone was described in 1991.[2] 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
- ↑ 1.0 1.1 1.2 "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. October 2011. doi:10.2174/138945011798109509. PMID 21561420.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza". Neuroscience Letters 127 (2): 237–241. June 1991. doi:10.1016/0304-3940(91)90802-z. PMID 1652718.
- ↑ 3.0 3.1 "The structure of rosmariquinone — A new antioxidant isolated from Rosmarinus officinalis L.". Journal of the American Oil Chemists' Society 62 (1): 96–98. 1985. doi:10.1007/BF02541500. ISSN 0003-021X. https://aocs.onlinelibrary.wiley.com/doi/10.1007/BF02541500. Retrieved 1 October 2025.
- ↑ "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. June 2004. doi:10.1016/j.ejphar.2004.04.021. PMID 15212961.
- ↑ 5.0 5.1 "GABA(A) receptor channel pharmacology". Current Pharmaceutical Design 11 (15): 1867–1885. 2005. doi:10.2174/1381612054021024. PMID 15974965.
- ↑ 6.0 6.1 "The structure of miltirone, a new diterpenoid quinone". Journal of the Chemical Society D: Chemical Communications (5): 299a. 1970. doi:10.1039/c2970000299a. ISSN 0577-6171. https://xlink.rsc.org/?DOI=c2970000299a. Retrieved 1 October 2025.
- ↑ "Miltirone". 1 February 2013. https://adisinsight.springer.com/drugs/800003466.
- ↑ "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. May 1991. doi:10.1021/jm00109a022. PMID 1851844.
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