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The N-methyl-D-aspartatereceptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and kainate receptors. Depending on its subunit composition, its ligands are glutamate and glycine (or D-serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Mg2+ ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a “coincidence detector” and only once both of these conditions are met, the channel opens and it allows positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions.
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist.
5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.
The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Accurate regulation of GABAergic transmission through appropriate developmental processes, specificity to neural cell types, and responsiveness to activity is crucial for the proper functioning of nearly all aspects of the central nervous system (CNS). Upon opening, the GABAA receptor on the postsynaptic cell is selectively permeable to chloride ions (Cl−) and, to a lesser extent, bicarbonate ions (HCO3−).
The glycine receptor is the receptor of the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem.
The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5.
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.
The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP for its ligand ketazocine, is a G protein-coupled receptor that in humans is encoded by the OPRK1 gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind opioid-like compounds in the brain and are responsible for mediating the effects of these compounds. These effects include altering nociception, consciousness, motor control, and mood. Dysregulation of this receptor system has been implicated in alcohol and drug addiction.
Neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin. Two of the receptors encoded by the NTSR1 and NTSR2 genes contain seven transmembrane helices and are G protein coupled. Numerous crystal structures have been reported for the neurotensin receptor 1 (NTS1). The third receptor has a single transmembrane domain and is encoded by the SORT1 gene.
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.
Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene.
Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.
A convulsant is a drug which induces convulsions and/or epileptic seizures, the opposite of an anticonvulsant. These drugs generally act as stimulants at low doses, but are not used for this purpose due to the risk of convulsions and consequent excitotoxicity. Most convulsants are antagonists at either the GABAA or glycine receptors, or ionotropic glutamate receptor agonists. Many other drugs may cause convulsions as a side effect at high doses but only drugs whose primary action is to cause convulsions are known as convulsants. Nerve agents such as sarin, which were developed as chemical weapons, produce convulsions as a major part of their toxidrome, but also produce a number of other effects in the body and are usually classified separately. Dieldrin which was developed as an insecticide blocks chloride influx into the neurons causing hyperexcitability of the CNS and convulsions. The Irwin observation test and other studies that record clinical signs are used to test the potential for a drug to induce convulsions. Camphor, and other terpenes given to children with colds can act as convulsants in children who have had febrile seizures.
S-15535 is a phenylpiperazine drug which is a potent and highly selective 5-HT1A receptor ligand that acts as an agonist and antagonist at the presynaptic and postsynaptic 5-HT1A receptors, respectively. It has anxiolytic properties.
DCG-IV is a research drug which acts as a group-selective agonist for the group II metabotropic glutamate receptors (mGluR2/3). It has potent neuroprotective and anticonvulsant effects in animal studies, as well as showing anti-Parkinsonian effects, but also impairs the formation of memories.
Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.
Pitrazepin is a competitive GABAA and glycine receptor antagonist. It has been used to study insect and snail nervous systems in scientific research.
Quisqualamine is the α-decarboxylated analogue of quisqualic acid, as well as a relative of the neurotransmitters glutamate and γ-aminobutyric acid (GABA). α-Decarboxylation of excitatory amino acids can produce derivatives with inhibitory effects. Indeed, unlike quisqualic acid, quisqualamine has central depressant and neuroprotective properties and appears to act predominantly as an agonist of the GABAA receptor and also to a lesser extent as an agonist of the glycine receptor, due to the facts that its actions are inhibited in vitro by GABAA antagonists like bicuculline and picrotoxin and by the glycine antagonist strychnine, respectively. Mg2+ and DL-AP5, NMDA receptor blockers, CNQX, an antagonist of both the AMPA and kainate receptors, and 2-hydroxysaclofen, a GABAB receptor antagonist, do not affect quisqualamine's actions in vitro, suggesting that it does not directly affect the ionotropic glutamate receptors or the GABAB receptor in any way. Whether it binds to and acts upon any of the metabotropic glutamate receptors like its analogue quisqualic acid however is unclear.
HA-966 or (±)-3-amino-1-hydroxy-pyrrolidin-2-one is a molecule used in scientific research as a glycine receptor and NMDA receptor antagonist / low efficacy partial agonist. It has neuroprotective and anticonvulsant, anxiolytic, antinociceptive and sedative / hypnotic effects in animal models. Pilot human clinical trials in the early 1960s showed that HA-966 appeared to benefit patients with tremors of extrapyramidal origin.
References
- ↑ Miyakawa, N; Uchino, S; Yamashita, T; Okada, H; Nakamura, T; Kaminogawa, S; Miyamoto, Y; Hisatsune, T (16 September 2002). "A glycine receptor antagonist, strychnine, blocked NMDA receptor activation in the neonatal mouse neocortex". NeuroReport. 13 (13): 1667–73. doi:10.1097/00001756-200209160-00020. PMID 12352624. S2CID 34027498.
- ↑ Vandenberg, RJ; Handford, CA; Schofield, PR (September 1992). "Distinct agonist- and antagonist-binding sites on the glycine receptor". Neuron. 9 (3): 491–6. doi:10.1016/0896-6273(92)90186-h. PMID 1326295. S2CID 45100334.
