Pesampator (; developmental code names BIIB-104 and PF-04958242) 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 is under development by

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

for the treatment of cognitive symptoms in

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

. It was also under development for the treatment of age-related sensorineural hearing loss, but development for this indication was terminated due to insufficient effectiveness. As of July 2018, pesampator is in 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 for cognitive symptoms in schizophrenia. Pesampator 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 mibampator (LY-451395) among others. It is described as a "high-impact" AMPAR PAM, unlike so-called "low-impact" AMPAR PAMs 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 cogener

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). In animals, low doses of pesampator have been found to 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 ...

, whereas higher doses produce motor coordination disruptions and convulsions. The same effects, as well as

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, have been observed with orthosteric and other high-impact allosteric AMPAR activators. In healthy volunteers, pesampator has been found to significantly reduce

ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ...

-induced deficits in

verbal learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machines; there is also evidence for some kind of learni ...

and

working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...

without attenuating ketamine-induced

psychotomimetic A drug with psychotomimetic (also known as psychotogenic) actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to only hallucinations. Psychotomimesis is the onset of psychotic symptoms following the administrati ...

effects. It was able to complete reverse ketamine-induced impairments in

spatial working memory In cognitive psychology and neuroscience, spatial memory is a form of memory responsible for the recording and recovery of information needed to plan a course to a location and to recall the location of an object or the occurrence of an event. S ...

in the participants. In addition to its actions on the AMPAR, pesampator has been reported to act as a

GlyT1 Sodium- and chloride-dependent glycine transporter 1, also known as glycine transporter 1, is a protein that in humans is encoded by the ''SLC6A9'' gene. Selective inhibitors Elevation of extracellular synaptic glycine concentration by blockade of ...

glycine transporter Glycine transporters (GlyTs) are plasmalemmal neurotransmitter transporters. They serve to terminate the signaling of glycine by mediating its reuptake from the synaptic cleft back into the presynaptic neurons. There are two glycine transporters ...

blocker. As such, it is also a

glycine reuptake inhibitor A glycine reuptake inhibitor (GRI) is a type of drug which inhibits the reuptake of the neurotransmitter glycine by blocking one or more of the glycine transporters (GlyTs). Examples of GRIs include bitopertin (RG1678), Org 24598, Org 25935, AL ...

, and may act indirectly to activate the glycine receptor and the

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...

co-agonist

site Site most often refers to: * Archaeological site * Campsite, a place used for overnight stay in an outdoor area * Construction site * Location, a point or an area on the Earth's surface or elsewhere * Website, a set of related web pages, typical ...

of the NMDA receptor by increasing

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

levels of

References

{{Ionotropic glutamate receptor modulators AMPA receptor positive allosteric modulators Experimental drugs Glycine reuptake inhibitors Nitriles Nootropics Sulfonamides Tetrahydrofurans Thiophenes

See also

References