Ampakines, also stylized as AMPAkines, are a subgroup of AMPA receptor positive allosteric modulators with a benzamide or closely related chemical structure. They are also known as "CX compounds". Ampakines take their name from the AMPA receptor (AMPAR), a type of ionotropic glutamate receptor with which the ampakines interact and act as positive allosteric modulators (PAMs) of. Although all ampakines are AMPAR PAMs, not all AMPAR PAMs are ampakines.
CX717 is an ampakine compound created by Christopher Marrs and Gary Rogers in 1996 at Cortex Pharmaceuticals. It affects the neurotransmitter glutamate, with trials showing the drug improves cognitive functioning and memory.
Tianeptine, sold under the brand names Stablon and Coaxil among others, is an atypical tricyclic antidepressant which is used mainly in the treatment of major depressive disorder, although it may also be used to treat anxiety, asthma, and irritable bowel syndrome.
Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to treat postpartum depression. It is given by injection into a vein.
CX-614 is an ampakine drug developed by Cortex Pharmaceuticals. It has been investigated for its effect on AMPA receptors.
The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a protein that, in humans, is encoded by the CHRM4 gene.
Metabotropic glutamate receptor 2 (mGluR2) is a protein that, in humans, is encoded by the GRM2 gene. mGluR2 is a G protein-coupled receptor (GPCR) that couples with the Gi alpha subunit. The receptor functions as an autoreceptor for glutamate, that upon activation, inhibits the emptying of vesicular contents at the presynaptic terminal of glutamatergic neurons.
IDRA-21 is a positive allosteric modulator of the AMPA receptor and a benzothiadiazine derivative. It is a chiral molecule, with (+)-IDRA-21 being the active form.
LY-503430 is an AMPA receptor positive allosteric modulator developed by Eli Lilly.
LY-341495 is a research drug developed by the pharmaceutical company Eli Lilly, which acts as a potent and selective orthosteric antagonist for the group II metabotropic glutamate receptors (mGluR2/3).
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.
AMN082 is a selective metabotropic glutamate receptor 7 (mGluR7) allosteric agonist. It mimics the effect of glutamate. AMN082 is the first selective mGluR7 agonist and has expanded the potential array of research opportunities on the effects of mGluR7 in the central nervous system.
2-Methyl-6-(phenylethynyl)pyridine (MPEP) is a research drug which was one of the first compounds found to act as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. After being originally patented as a liquid crystal for LCDs, it was developed by the pharmaceutical company Novartis in the late 1990s. It was found to produce neuroprotective effects following acute brain injury in animal studies, although it was unclear whether these results were purely from mGluR5 blockade as it also acts as a weak NMDA antagonist, and as a positive allosteric modulator of another subtype mGlu4, and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons. It was also shown to produce antidepressant and anxiolytic effects in animals, and to reduce the effects of morphine withdrawal, most likely due to direct interaction between mGluR5 and the μ-opioid receptor.
GS-39783 is a compound used in scientific research which acts as a positive allosteric modulator at the GABAB receptor. It has been shown to produce anxiolytic effects in animal studies, and reduces self-administration of alcohol, cocaine and nicotine.
LY-487,379 is a drug used in scientific research that acts as a selective positive allosteric modulator for the metabotropic glutamate receptor group II subtype mGluR2. It is used to study the structure and function of this receptor subtype, and LY-487,379 along with various other mGluR2/3 agonists and positive modulators are being investigated as possible antipsychotic and anxiolytic drugs.
S-18986 is a positive allosteric modulator of the AMPA receptor related to cyclothiazide. It has nootropic and neuroprotective effects in animal studies, and induces both production of BDNF and AMPA-mediated release of noradrenaline and acetylcholine in the hippocampus and frontal cortex of the brain.
CBiPES is a drug used in scientific research that acts as a selective positive allosteric modulator for the metabotropic glutamate receptor group II subtype mGluR2. It has potentially antipsychotic effects in animal models, and is used for researching the role of mGluR2 receptors in schizophrenia and related disorders.
Tulrampator is a positive allosteric modulator (PAM) of the AMPA receptor (AMPAR), an ionotropic glutamate receptor, which is under development by RespireRx Pharmaceuticals and Servier for the treatment of major depressive disorder, Alzheimer's disease, dementia, and mild cognitive impairment. Tulrampator was in phase II clinical trial for depression, but failed to show superiority over placebo. There are also phase II clinical trials for Alzheimer's disease and phase I trials for dementia and mild cognitive impairment.
AMPA receptor positive allosteric modulators are positive allosteric modulators (PAMs) of the AMPA receptor (AMPR), a type of ionotropic glutamate receptor which mediates most fast synaptic neurotransmission in the central nervous system.
TAK-653 is an experimental drug being investigated as a treatment for treatment-resistant depression. It is being developed by Takeda.
