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]
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]
^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.
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10.1016/j.neuropharm.2003.07.002.
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^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.