IDRA-21

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IDRA-21
Systematic (IUPAC) name
7-chloro-3-methyl-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide
Identifiers
CAS number 163936-78-5
ATC code  ?
PubChem 3688
Chemical data
Formula C8H9ClN2O2S 
Mol. mass 232.68726 g/mol
SMILES eMolecules & PubChem
Synonyms IDRA-21
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.

?
Legal status

Investigational New Medicine
Routes  ?

IDRA-21 is an ampakine drug derived from aniracetam. IDRA-21 is a chiral molecule, with (+)-IDRA-21 being the active form.[1]

IDRA-21 shows nootropic effects in animal studies, significantly improving learning and memory. It is around 10-30x more potent than aniracetam in reversing cognitive deficits induced by alprazolam or scopolamine,[2][3] and produces sustained effects lasting for up to three days 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 does 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 benzoylpiperidine derived ampakine drugs, 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]


[edit] References

  1. ^ Uzunov DP, Zivkovich I, Pirkle WH, Costa E, Guidotti A. 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. 1995 Aug;84(8):937-42. PMID 7500277
  2. ^ Thompson DM, Guidotti A, DiBella M, Costa E. 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 U S A. 1995 Aug 15;92(17):7667-71. PMID 7644474
  3. ^ Zivkovic I, Thompson DM, Bertolino M, Uzunov D, DiBella M, Costa E, Guidotti A. 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. Journal of Pharmacology and Experimental Therapeutics. 1995 Jan;272(1):300-9. PMID 7815345
  4. ^ Buccafusco JJ, Weiser T, Winter K, Klinder K, Terry AV. The effects of IDRA 21, a positive modulator of the AMPA receptor, on delayed matching performance by young and aged rhesus monkeys. Neuropharmacology. 2004 Jan;46(1):10-22. PMID 14654093
  5. ^ Arai A, Guidotti A, Costa E, Lynch G. Effect of the AMPA receptor modulator IDRA 21 on LTP in hippocampal slices. Neuroreport. 1996 Sep 2;7(13):2211-5. PMID 8930991
  6. ^ Impagnatiello F, Oberto A, Longone P, Costa E, Guidotti A. 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 U S A. 1997 Jun 24;94(13):7053-8. PMID 9192690
  7. ^ Yamada KA, Covey DF, Hsu CY, Hu R, Hu Y, He YY. The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury. Annals of Neurology. 1998 May;43(5):664-9. PMID 9585363
  8. ^ Nagarajan N, Quast C, Boxall AR, Shahid M, Rosenmund C. Mechanism and impact of allosteric AMPA receptor modulation by the ampakine CX546. Neuropharmacology. 2001 Nov;41(6):650-63. PMID 11640919
  9. ^ Phillips D, Sonnenberg J, Arai AC, Vaswani R, Krutzik PO, Kleisli T, Kessler M, Granger R, Lynch G, Richard Chamberlin A. 5'-alkyl-benzothiadiazides: a new subgroup of AMPA receptor modulators with improved affinity. Bioorganic and Medicinal Chemistry. 2002 May;10(5):1229-48. PMID 11886787
  10. ^ Arai AC, Xia YF, Kessler M, Phillips D, Chamberlin R, Granger R, Lynch G. 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. 2002 Sep;62(3):566-77. PMID 12181433
  11. ^ Black MD. Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data. Psychopharmacology (Berlin). 2005 Apr;179(1):154-63. PMID 15672275


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Psychoanaleptics: psychostimulants, agents used for ADHD and nootropics (N06B)
Centrally acting sympathomimetics
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Racetams
Ampakines
Eugeroics
Histamine H3 receptor antagonists
Other psychostimulants and nootropics