IDRA-21 10mg – 60 capsules

IDRA-21 oral research capsules. IDRA-21 (7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide) is one of the most potent benzothiadiazide-class AMPA-receptor positive allosteric modulators (“ampakines”) ever characterized — approximately 10–30-fold more potent than aniracetam in standardized AMPA-receptor radioligand and electrophysiology assays, and the reference second-generation ampakine in two decades of cognitive-enhancement research from the laboratory of Gary Lynch at UC Irvine. While newer, even more potent ampakines have since been developed (CX-717, CX-1739, TAK-653), IDRA-21 retains its position as the most extensively published benchmark molecule for studying AMPA-PAM-driven LTP, BDNF release and cognitive enhancement in rodent models.

Research Overview

IDRA-21 is a second-generation benzothiadiazide ampakine — a positive allosteric modulator of the AMPA subtype of ionotropic glutamate receptors — first characterized in the early 1990s as part of the medicinal-chemistry program that produced the entire ampakine family at UC Irvine and later at Cortex Pharmaceuticals [1]. The molecule slows AMPA-receptor desensitization and deactivation, increasing the integrated excitatory postsynaptic current produced by a given glutamate release event without itself activating the receptor [1,2]. In behavioural studies, IDRA-21 produces dose-dependent enhancement of acquisition, consolidation and retrieval across passive-avoidance, delayed-matching-to-sample and spatial-memory paradigms in rodents and non-human primates, with documented increases in hippocampal LTP magnitude and BDNF release [1,2,3]. While newer, more potent ampakines (CX-717, TAK-653) have since superseded IDRA-21 in clinical development, IDRA-21 retains a unique position as the most extensively published benchmark molecule in AMPA-PAM cognitive-enhancement research — the canonical reference compound for ampakine pharmacology and the standard against which newer molecules are characterized.

Primary Research Areas

• AMPA-receptor positive allosteric modulation — the most extensively published second-generation benzothiadiazide ampakine; the standard reference compound for the entire AMPA-PAM class [1,2].
• LTP and synaptic plasticity — robust enhancement of hippocampal LTP magnitude and persistence in slice and in-vivo electrophysiology models [1].
• Cognitive enhancement research — dose-dependent improvement of memory acquisition, consolidation and retrieval across multiple rodent paradigms; documented effects in non-human primates [2,3].
• BDNF release and neurotrophic signaling — induces activity-dependent BDNF release in hippocampal slice and in vivo, the proposed downstream mediator of ampakine cognitive effects [2].
• Reference compound for newer ampakines — the canonical benchmark in structure-activity studies and head-to-head comparisons with later-generation molecules including CX-717 and TAK-653 [1,3].

References

1. Yamada KA. Therapeutic potential of positive AMPA receptor modulators in the treatment of neurological disease. Expert Opin Investig Drugs. 2000;9(4):765–778.
2. Zivkovic I, Thompson DM, Bertolino M, et al. 7-Chloro-3-methyl-3-4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21): a benzothiadiazine derivative that enhances cognition. J Pharmacol Exp Ther. 1995;272(1):300–309.
3. 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;46(1):10–22.