Miltirone

Last updated

Miltirone
Miltirone.svg
Clinical data
Other namesRosmariquinone
Routes of
administration 		Oral [1]
Drug class GABAA receptor positive allosteric modulator; Anxiolytic
ATC code
  • None
Identifiers
  • 8,8-dimethyl-2-propan-2-yl-6,7-dihydro-5H-phenanthrene-3,4-dione
CAS Number
PubChem CID
ChemSpider
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C19H22O2
Molar mass 282.383 g·mol−1
3D model (JSmol)
  • CC(C)C1=CC2=C(C3=C(C=C2)C(CCC3)(C)C)C(=O)C1=O
  • InChI=1S/C19H22O2/c1-11(2)14-10-12-7-8-15-13(6-5-9-19(15,3)4)16(12)18(21)17(14)20/h7-8,10-11H,5-6,9H2,1-4H3
  • Key:FEFAIBOZOKSLJR-UHFFFAOYSA-N

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]

Contents

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 Tooltip half-maximal inhibitory concentration) 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

  1. 1 2 3 4 5 6 7 8 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.
  2. 1 2 3 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.
  3. 1 2 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.
  4. ↑ 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.
  5. 1 2 Johnston GA (2005). "GABA(A) receptor channel pharmacology". Current Pharmaceutical Design. 11 (15): 1867–1885. doi:10.2174/1381612054021024. PMID   15974965.
  6. 1 2 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.
  7. ↑ "Miltirone". AdisInsight. 1 February 2013. Retrieved 1 October 2025.
  8. ↑ 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.
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