2 replies to this topic

[Reformed-Redan]

I'm not sure about the level of interest in AMPAkines. I already take a bunch of neuroprotective compounds, deprenyl, ALCAR, Bacopa so I see the risk of excitotoxicity as somewhat mitigated. IDRA-21 was not pushed forward because it was such a potent compound. It was intended for people with dementia or recovering from strokes. While compounds like NSI-189 are interesting for people with MDD, I don't see the need for it in the average citizen. NSI-189 insofar as I can tell was intended to be used on veterans recovering from extremely stressful situation, like war and helping with PTSD.

Also, I don't understand the interest in CX compounds and IDRA-21. IDRA-21 has a much longer half-life, lower dose profile and sustained nootropic effects after administration of the compound in patat monkeys. CX has not shown such properties to my knowledge. And, if people are scared of IDRA-21 because it has a benzo structure, that's just stupid. There are plenty of compounds with benzo structures that are potent nootropics, like GABAa alpha 5 inverse agonists and IDRA-21 which also acts as a moderate inverse agonist at those receptors. So, I don't see why the bad rap of benzo's should carry onto this compound (either that or people are misinformed.)

Still interested in your input on IDRA-21. So, fat a similar compound with such qualities is yet to be discovered.

[uglybuddy6]

I would like to see more research and what analogues could be made from this. It sounds like a very interesting compound and I would like to try some.

[FreeMyBrain]

Not sure if this is possibly a reason why IDRA-21 may not have not been pushed forward?

Ann Neurol. 1998 May;43(5):664-9.
The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury.

Yamada KA, Covey DF, Hsu CY, Hu R, Hu Y, He YY.

Source

Department of Neurology, St Louis Children's Hospital, MO, USA.

Abstract


The diazoxide derivative IDRA 21 and other positive modulators of (AMPA)-type glutamate receptors are considered potential memory-enhancing agents. However, AMPA receptor activation contributes to CA1 hippocampal neuron damage from global ischemia in rodents, raising the possibility that 7-chloro-3-methyl-3-4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21) or drugs with similar actions may worsen ischemic neuronal injury. Here we demonstrate that glutamate plus IDRA 21 kills cultured rat hippocampal neurons by AMPA receptor activation, and, in vivo, 12 and 24 mg/kg of IDRA 21 given orally increases CA1 neuron loss produced by 10 minutes of global ischemia. Treating patients with drugs that potentiate AMPA receptor activation will have to consider these potential effects, particularly when coexistent with conditions in which excessive activation of AMPA receptors may occur (eg, stroke, seizures).

PMID: 9585363 [PubMed - indexed for MEDLINE]