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 stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that ...

(PAM) 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 ...

(AMPAR), an ionotropic glutamate receptor, which was under development by

Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was a Union Army officer, pharmacist, chemist, and businessman who founded Eli Lilly and Company. Lilly enlisted in the Union Army during the American Civil War and recruited a company of men to ...

for the treatment of agitation/

aggression Aggression is behavior aimed at opposing or attacking something or someone. Though often done with the intent to cause harm, some might channel it into creative and practical outlets. It may occur either reactively or without provocation. In h ...

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

but was never marketed. It reached phase II

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

s prior to the discontinuation of its development. Mibampator belongs to the biarylpropylsulfonamide group of AMPAR PAMs, which also includes LY-404187, 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 and its congener farampator (CX-691, ORG-24448), and is able to elicit comparatively more robust increases in AMPAR signaling. In animals, high-impact AMPAR potentiators enhance

cognition Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

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 remembe ...

at low doses, but produce

motor coordination In physiology, motor coordination is the orchestrated movement of multiple body parts as required to accomplish intended actions, like walking. This coordination is achieved by adjusting kinematic and kinetic parameters associated with each bo ...

disruptions,

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...

s, 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 – specifical ...

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, bacteria, bacterium, or plant, as well as the effect o ...

, 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