Mibampator (developmental code name LY-451395) 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 stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

(PAM) of the AMPA receptor (AMPAR), an

ionotropic glutamate receptor Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players in ...

, which was under development by

Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and ...

for the treatment of agitation/ aggression in Alzheimer's disease but was never marketed. It reached phase II

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s prior to the discontinuation of its development. Mibampator belongs to the

biarylpropylsulfonamide AMPA receptor positive allosteric modulators are positive allosteric modulators (PAMs) of the receptor (AMPR), a type of ionotropic glutamate receptor which mediates most fast synaptic neurotransmission in the central nervous system. Medic ...

group of AMPAR PAMs, which also includes

LY-404187 LY-404187 is an AMPA receptor positive allosteric modulator which was developed by Eli Lilly and Company. It is a member of the biarylpropylsulfonamide class of AMPA receptor potentiators. LY-404187 has been demonstrated to enhance cognitive f ...

, LY-503430, and PF-04958242 among others. It is a "high-impact" AMPAR potentiator, unlike "low-impact" AMPAR potentiators from other classes like

CX-516 CX-516 is an ampakine and nootropic that acts as an AMPA receptor positive allosteric modulator and had been undergoing development by a collaboration between Cortex, Shire, and Servier. It was studied as a potential treatment for Alzheimer' ...

and its congener

farampator Farampator (developmental code names CX-691, ORG-24448, SCH-900460) is an ampakine drug. It was developed by Cortex Pharmaceuticals, and licensed to Organon BioSciences for commercial development. Following the purchase of Organon by Schering-P ...

(CX-691, ORG-24448), and is able to elicit comparatively more robust increases in AMPAR signaling. In animals, high-impact AMPAR potentiators enhance cognition and

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered ...

at low doses, but produce motor coordination disruptions, convulsions, and

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 – specificall ...

at higher doses. Mibampator failed to produce cognitive improvement in patients with Alzheimer's disease, though it did show improvements in neuropsychiatric measures. A caveat of the study was that the maximally tolerated dosage of the drug could not be used due to

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...

, and dosages in the same range in rodents notably failed to improve memory-related behavior.

References

External links

Mibampator - AdisInsight
Abandoned drugs AMPA receptor positive allosteric modulators Nootropics Sulfonamides {{Nervous-system-drug-stub

See also

References

External links