Tulrampator (developmental code names S-47445, CX-1632) 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 The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the ce ...

(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 RespireRx Pharmaceuticals (formerly Cortex Pharmaceuticals) and

Servier Servier Laboratories (French: Laboratoires Servier, often abbreviated to Servier) is an international pharmaceutical company governed by a non-profit foundation, with its headquarters in France (Suresnes). The consolidated turnover for the 201 ...

for the treatment of

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...

(as an

adjunct Adjunct may refer to: * Adjunct (grammar), words used as modifiers * Adjunct professor, a rank of university professor * Adjuncts, sources of sugar used in brewing * Adjunct therapy used to complement another main therapeutic agent, either to impr ...

), Alzheimer's disease,

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

, and

mild cognitive impairment Mild cognitive impairment (MCI) is a neurocognitive disorder which involves cognitive impairments beyond those expected based on an individual's age and education but which are not significant enough to interfere with instrumental activities of ...

. Tulrampator was in 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 ...

for depression, but failed to show superiority over placebo.https://clinicaltrials.servier.com/wp-content/uploads/CL2-47445-014-synopsis-report.pdf There are also phase II clinical trials for Alzheimer's disease and phase I trials for dementia and mild cognitive impairment. Tulrampator is a "high-impact" AMPAR potentiator, unlike "low-impact" AMPAR potentiators like CX-516 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-Pl ...

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

cognition Cognition refers to "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, thoug ...

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 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 body part involved i ...

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 sometimes used as a ...

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. Tulrampator itself has been found in animals to enhance cognition and memory, to produce

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness ...

antianhedonic Anhedonia is a diverse array of deficits in hedonic function, including reduced motivation or ability to experience pleasure. While earlier definitions emphasized the inability to experience pleasure, anhedonia is currently used by researchers t ...

-, and

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

-like effects, and to have

neurotrophic Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and differentiation of both developing and mature neurons. Most NTFs exert their tro ...

and

neuroplasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it ...

-promoting activities. Moreover, it has been found to increase levels of

brain-derived neurotrophic factor Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canon ...

(BDNF) in the

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

and to stimulate hippocampal

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs ...

. The rapidly-acting

effects of the

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induc ...

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 ...

appear to be mediated through indirect/downstream activation of AMPARs. This is evidenced by the fact that its antidepressant-like effects in animals are blocked by the AMPAR antagonist

NBQX NBQX (2,3-dioxo-6-nitro-7-sulfamoyl-benzo uinoxaline) is an antagonist of the AMPA receptor. NBQX blocks AMPA receptors in micromolar concentrations (~10–20 μM) and also blocks kainate receptors. In experiments, it is used to counter glutamate ...

. As such, tulrampator may be a rapid-acting antidepressant similarly to ketamine but without its

dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...

hallucinogen Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...

ic and certain other

adverse effect An adverse effect is an undesired harmful effect resulting from a Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...

s (e.g.,

urotoxicity Urinary bladder disease includes urinary bladder inflammation such as cystitis, bladder rupture and bladder obstruction (tamponade). Cystitis is common, sometimes referred to as urinary tract infection (UTI) caused by bacteria, bladder rupture ...

References

External links

Tulrampator (S-47445, CX-1632) - AdisInsight

Tulrampator (S-47445, CX-1632) - Alzforum
{{Ionotropic glutamate receptor modulators AMPA receptor positive allosteric modulators Ampakines Antidepressants Anxiolytics Cyclopropanes Experimental drugs Fluoroarenes Heterocyclic compounds with 3 rings Nootropics Oxazines Triazines

See also

References

External links