Chemistry:IDRA-21
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| Formula | C8H9ClN2O2S |
| Molar mass | 232.68 g·mol−1 |
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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 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
- ↑ "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. August 1995. doi:10.1002/jps.2600840807. PMID 7500277.
- ↑ "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. August 1995. doi:10.1073/pnas.92.17.7667. PMID 7644474. Bibcode: 1995PNAS...92.7667T.
- ↑ "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. January 1995. PMID 7815345. http://jpet.aspetjournals.org/content/272/1/300.abstract.
- ↑ "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. January 2004. doi:10.1016/j.neuropharm.2003.07.002. PMID 14654093.
- ↑ "Effect of the AMPA receptor modulator IDRA 21 on LTP in hippocampal slices". NeuroReport 7 (13): 2211–5. September 1996. doi:10.1097/00001756-199609020-00031. PMID 8930991.
- ↑ "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. June 1997. doi:10.1073/pnas.94.13.7053. PMID 9192690. Bibcode: 1997PNAS...94.7053I.
- ↑ "The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury". Annals of Neurology 43 (5): 664–9. May 1998. doi:10.1002/ana.410430517. PMID 9585363.
- ↑ "Mechanism and impact of allosteric AMPA receptor modulation by the ampakine CX546". Neuropharmacology 41 (6): 650–63. November 2001. doi:10.1016/S0028-3908(01)00133-2. PMID 11640919.
- ↑ "5'-alkyl-benzothiadiazides: a new subgroup of AMPA receptor modulators with improved affinity". Bioorganic & Medicinal Chemistry 10 (5): 1229–48. May 2002. doi:10.1016/S0968-0896(01)00405-9. PMID 11886787.
- ↑ "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. September 2002. doi:10.1124/mol.62.3.566. PMID 12181433.
- ↑ "Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data". Psychopharmacology 179 (1): 154–63. April 2005. doi:10.1007/s00213-004-2065-6. PMID 15672275.
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