IDRA-21

IDRA-21 is a positive allosteric modulator of the AMPA receptor and a benzothiadiazine derivative. It is a chiral molecule, with (+)-IDRA-21 being the active form.[1]

IDRA-21
Legal status
Legal status
Identifiers
IUPAC name
  • 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC8H9ClN2O2S
Molar mass232.68 g·mol−1
3D model (JSmol)
SMILES
  • CC1NC2=C(C=C(C=C2)Cl)S(=O)(=O)N1
InChI
  • InChI=1S/C8H9ClN2O2S/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5/h2-5,10-11H,1H3 N
  • Key:VZRNTCHTJRLTMU-UHFFFAOYSA-N N
 NY (what is this?)  (verify)

IDRA-21 shows nootropic effects in animal studies, significantly improving learning and memory. It is around 10–30 times more potent than aniracetam in reversing cognitive deficits induced by alprazolam or scopolamine,[2][3] and produces sustained effects lasting for up to 48 hours after a single dose.[4] The mechanism for this action is thought to be through promoting the induction of long-term potentiation between synapses in the brain.[5]

IDRA-21 may not produce neurotoxicity under normal conditions,[6] although it may worsen neuronal damage following global ischemia after stroke or seizures.[7]

In comparison to the ampakines or benzoylpiperidine-derived AMPA receptor potentiators, IDRA-21 was more potent than CX-516, but less potent than CX-546.[8] Newer benzothiadiazide derivatives with greatly increased potency compared to IDRA-21 have been developed,[9][10] but these have not been researched to the same extent, with the benzoylpiperidine and benzoylpyrrolidine CX-series of drugs being favoured for clinical development, most likely due to more favourable toxicity profiles at high doses.[11]

See also

References
  1. Uzunov DP, Zivkovich I, Pirkle WH, Costa E, Guidotti A (August 1995). "Enantiomeric resolution with a new chiral stationary phase of 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide, a cognition-enhancing benzothiadiazine derivative". Journal of Pharmaceutical Sciences. 84 (8): 937–42. doi:10.1002/jps.2600840807. PMID 7500277.
  2. Thompson DM, Guidotti A, DiBella M, Costa E (August 1995). "7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys". Proceedings of the National Academy of Sciences of the United States of America. 92 (17): 7667–71. Bibcode:1995PNAS...92.7667T. doi:10.1073/pnas.92.17.7667. PMC 41206. PMID 7644474.
  3. Zivkovic I, Thompson DM, Bertolino M, Uzunov D, DiBella M, Costa E, Guidotti A (January 1995). "7-Chloro-3-methyl-3-4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21): a benzothiadiazine derivative that enhances cognition by attenuating DL-alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor desensitization". The Journal of Pharmacology and Experimental Therapeutics. 272 (1): 300–9. PMID 7815345.
  4. Buccafusco JJ, Weiser T, Winter K, Klinder K, Terry AV (January 2004). "The effects of IDRA 21, a positive modulator of the AMPA receptor, on delayed matching performance by young and aged rhesus monkeys". Neuropharmacology. 46 (1): 10–22. doi:10.1016/j.neuropharm.2003.07.002. PMID 14654093. S2CID 26443642.
  5. Arai A, Guidotti A, Costa E, Lynch G (September 1996). "Effect of the AMPA receptor modulator IDRA 21 on LTP in hippocampal slices". NeuroReport. 7 (13): 2211–5. doi:10.1097/00001756-199609020-00031. PMID 8930991. S2CID 35888339.
  6. Impagnatiello F, Oberto A, Longone P, Costa E, Guidotti A (June 1997). "7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide: a partial modulator of AMPA receptor desensitization devoid of neurotoxicity". Proceedings of the National Academy of Sciences of the United States of America. 94 (13): 7053–8. Bibcode:1997PNAS...94.7053I. doi:10.1073/pnas.94.13.7053. PMC 21283. PMID 9192690.
  7. Yamada KA, Covey DF, Hsu CY, Hu R, Hu Y, He YY (May 1998). "The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury". Annals of Neurology. 43 (5): 664–9. doi:10.1002/ana.410430517. PMID 9585363. S2CID 39977647.
  8. Nagarajan N, Quast C, Boxall AR, Shahid M, Rosenmund C (November 2001). "Mechanism and impact of allosteric AMPA receptor modulation by the ampakine CX546". Neuropharmacology. 41 (6): 650–63. doi:10.1016/S0028-3908(01)00133-2. PMID 11640919. S2CID 7796112.
  9. Phillips D, Sonnenberg J, Arai AC, Vaswani R, Krutzik PO, Kleisli T, et al. (May 2002). "5'-alkyl-benzothiadiazides: a new subgroup of AMPA receptor modulators with improved affinity". Bioorganic & Medicinal Chemistry. 10 (5): 1229–48. CiteSeerX 10.1.1.113.7845. doi:10.1016/S0968-0896(01)00405-9. PMID 11886787.
  10. Arai AC, Xia YF, Kessler M, Phillips D, Chamberlin R, Granger R, Lynch G (September 2002). "Effects of 5'-alkyl-benzothiadiazides on (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor biophysics and synaptic responses". Molecular Pharmacology. 62 (3): 566–77. doi:10.1124/mol.62.3.566. PMID 12181433.
  11. Black MD (April 2005). "Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data". Psychopharmacology. 179 (1): 154–63. doi:10.1007/s00213-004-2065-6. PMID 15672275. S2CID 5869366.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.