IDRA-21 showsnootropic effects in animal studies, significantly improving learning and memory. It is around 10–30 times more potent thananiracetam in reversingcognitive deficits induced byalprazolam orscopolamine,[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 oflong-term potentiation betweensynapses in the brain.[5]
In comparison to the ampakines orbenzoylpiperidine-derived AMPA receptor potentiators, IDRA-21 was more potent thanCX-516, but less potent thanCX-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]
^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.PMID7500277.
^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.PMID14654093.S2CID26443642.
^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.PMID9585363.S2CID39977647.
^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.PMID11640919.S2CID7796112.
^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.CiteSeerX10.1.1.113.7845.doi:10.1016/S0968-0896(01)00405-9.PMID11886787.
^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.PMID12181433.S2CID16182942.
^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.PMID15672275.S2CID5869366.
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