IDRA-21 is a

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that ...

of the

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitator ...

and a benzothiadiazine derivative. It is a chiral molecule, with (+)-IDRA-21 being the active form. IDRA-21 shows

nootropic Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...

effects in animal studies, significantly improving learning and memory. It is around 10–30 times more potent than

aniracetam Aniracetam (brand names Draganon, Sarpul, Ampamet, Memodrin, Referan), also known as ''N''-anisoyl-2-pyrrolidinone, is a racetam which is sold in Europe as a prescription drug. It is not approved by the Food and Drug Administration for use in t ...

in reversing cognitive deficits induced by

alprazolam Alprazolam, sold under the brand name Xanax among others, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly prescribed in the ...

scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ...

, and produces sustained effects lasting for up to 48 hours after a single dose. The mechanism for this action is thought to be through promoting the induction of

long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neuron ...

between

synapses In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

in the brain. IDRA-21 may not produce

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

under normal conditions, although it may worsen neuronal damage following global

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

after

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

. 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. Newer benzothiadiazide derivatives with greatly increased potency compared to IDRA-21 have been developed, 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.

References

{{Ionotropic glutamate receptor modulators AMPA receptor positive allosteric modulators Benzothiadiazines Chloroarenes Experimental drugs Nootropics

See also

References