IDRA-21

drugbox
IUPAC_name = 7-chloro-3-methyl-3,4-dihydro-2H-benzo [e] [1,2,4] thiadiazine 1,1-dioxide


width = 200
CAS_number = 163936-78-5
synonyms = IDRA-21
ATC_prefix =
ATC_suffix =
PubChem = 3688
DrugBank =
C = 8 | H = 9 | Cl = 1 | N = 2 | O = 2 | S = 1
molecular_weight = 232.68726 g/mol
smiles = CC1NC2=C(C=C(C=C2)Cl)S(=O)(=O)N1
bioavailability =
protein_bound =
metabolism =
elimination_half-life =
excretion =
pregnancy_AU =
pregnancy_US =
pregnancy_category=
legal_AU =
legal_CA =
legal_UK =
legal_US =
legal_status = Investigational New Medicine
routes_of_administration =

IDRA-21 is an ampakine drug derived from aniracetam. IDRA-21 is a chiral molecule, with (+)-IDRA-21 being the active form. [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. [http://www.ncbi.nlm.nih.gov/pubmed/7500277 PMID 7500277] ]

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, [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. [http://www.ncbi.nlm.nih.gov/pubmed/7644474 PMID 7644474] ] [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. [http://www.ncbi.nlm.nih.gov/pubmed/7815345 PMID 7815345] ] and produces sustained effects lasting for up to three days after a single dose. [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. [http://www.ncbi.nlm.nih.gov/pubmed/14654093 PMID 14654093] ] The mechanism for this action is thought to be through promoting the induction of long-term potentiation between synapses in the brain. [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. [http://www.ncbi.nlm.nih.gov/pubmed/8930991 PMID 8930991] ]

IDRA-21 does not produce neurotoxicity under normal conditions, [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. [http://www.ncbi.nlm.nih.gov/pubmed/9192690 PMID 9192690] ] although it may worsen neuronal damage following global ischemia after stroke or seizures. [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. [http://www.ncbi.nlm.nih.gov/pubmed/9585363 PMID 9585363] ]

In comparison to the benzoylpiperidine derived ampakine drugs, IDRA-21 was more potent than CX-516, but less potent than CX-546. [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. [http://www.ncbi.nlm.nih.gov/pubmed/11640919 PMID 11640919] ] Newer benzothiadiazide derivatives with greatly increased potency compared to IDRA-21 have been developed, [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. [http://www.ncbi.nlm.nih.gov/pubmed/11886787 PMID 11886787] ] [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. [http://www.ncbi.nlm.nih.gov/pubmed/12181433 PMID 12181433] ] 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. [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. [http://www.ncbi.nlm.nih.gov/pubmed/15672275 PMID 15672275] ]

References


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • idră — ÍDRĂ, idre, s.f. v. hidră. Trimis de gall, 13.09.2007. Sursa: DEX 98  ÍDRĂ s.f. v. hidră. Trimis de LauraGellner, 13.09.2007. Sursa: DN …   Dicționar Român

  • idra — s.f. [dal lat. hydra, gr. hýdra, der. di hýdōr acqua ]. 1. (mitol.) [mostruoso serpente (propr. Idra di Lerna ) con molte teste, le quali rinascevano se tagliate]. 2. (fig., non com.) [male dannoso alla società, difficile da estirpare: l i. della …   Enciclopedia Italiana

  • idra — idra, idre obs. ff. hydra …   Useful english dictionary

  • Idra — The Idra, which means threshing floor in Aramaic, is a Kabbalistic work included in printings of the Zohar, and was probably written and appended to the main body of the Zohar at a later date. Contemporary scholars believe the Idra dates to the… …   Wikipedia

  • IDRA — Cette page d’homonymie répertorie les différents sujets et articles partageant un même nom.   Sigles d’une seule lettre   Sigles de deux lettres   Sigles de trois lettres > Sigles de quatre lettres …   Wikipédia en Français

  • idra — ì·dra s.f. 1a. TS mitol. nella mitologia classica, mostruoso serpente con molteplici teste che rinascevano quando venivano tagliate, dalle cui gole usciva un alito così mefitico che chiunque si avvicinava moriva asfissiato 1b. TS numism. moneta d …   Dizionario italiano

  • idra — {{hw}}{{idra}}{{/hw}}s. f. 1 Nell antica mitologia greco romana, mostruoso serpente con molte teste, che, tagliate, rinascevano: l idra di Lerna. 2 (zool.) Piccolo animale dei Celenterati di acqua dolce a forma di polipo con lunghi tentacoli, che …   Enciclopedia di italiano

  • Idra — Sp Idrà Ap Ύδρα/Ydra L s. Egėjo j. ir mst. joje, PR Graikija …   Pasaulio vietovardžiai. Internetinė duomenų bazė

  • IDRA — infectious disease risk assessment …   Military dictionary

  • Idra — Hydra (Ydra) Δήμος Ύδρας (Ύδρα) DEC …   Deutsch Wikipedia


Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.