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| Formula | C17H17N3O2 |
| Molar mass | 295.336 g·mol−1 |
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Divaplon (RU-32698) is a nonbenzodiazepine, anxiolytic and anticonvulsant drug from the imidazopyrimidine family of drugs. It acts as a partial agonist at the "benzodiazepine site" of the GABAA receptor in the brain. [1] [2] [3]
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. Upon opening, the GABAA receptor on the postsynaptic cell is selectively permeable to chloride ions (Cl−) and, to a lesser extent, bicarbonate ions (HCO3−). Depending on the membrane potential and the ionic concentration difference, this can result in ionic fluxes across the pore. If the membrane potential is higher than the equilibrium potential (also known as the reversal potential) for chloride ions, when the receptor is activated Cl− will flow into the cell. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring at the postsynaptic cell. The reversal potential of the GABAA-mediated inhibitory postsynaptic potential (IPSP) in normal solution is −70 mV, contrasting the GABAB IPSP (-100 mV).
Alpidem, sold under the brand name Ananxyl, is a nonbenzodiazepine anxiolytic medication which was briefly used to treat anxiety disorders but is no longer marketed. It was previously marketed in France, but was discontinued due to liver toxicity. Alpidem is taken by mouth.
Bretazenil (Ro16-6028) is an imidazopyrrolobenzodiazepine anxiolytic drug which is derived from the benzodiazepine family, and was invented in 1988. It is most closely related in structure to the GABA antagonist flumazenil, although its effects are somewhat different. It is classified as a high-potency benzodiazepine due to its high affinity binding to benzodiazepine binding sites where it acts as a partial agonist. Its profile as a partial agonist and preclinical trial data suggests that it may have a reduced adverse effect profile. In particular bretazenil has been proposed to cause a less strong development of tolerance and withdrawal syndrome. Bretazenil differs from traditional 1,4-benzodiazepines by being a partial agonist and because it binds to α1, α2, α3, α4, α5 and α6 subunit containing GABAA receptor benzodiazepine receptor complexes. 1,4-benzodiazepines bind only to α1, α2, α3 and α5GABAA benzodiazepine receptor complexes.
DMCM is a drug from the β-carboline family. It acts as a negative allosteric modulator of GABAA receptors, meaning that it causes the opposite effects to the benzodiazepine class of drugs. As such, DMCM has anxiogenic and convulsant properties, and is used in scientific research to induce anxiety so that new anxiolytic medications can be tested, and to produce convulsions so that anticonvulsant medications can be tested. It has also been shown to produce analgesic effects in animals, thought to be because it produces panic which reduces the perception of pain.
Imidazenil is an experimental anxiolytic drug which is derived from the benzodiazepine family, and is most closely related to other imidazobenzodiazepines such as midazolam, flumazenil, and bretazenil.
Abecarnil (ZK-112,119) is an anxiolytic drug from the β-Carboline family. It is one of a relatively recently developed class of medicines known as the nonbenzodiazepines, which have similar effects to the older benzodiazepine group, but with quite different chemical structures. It is a partial agonist acting selectively at the benzodiazepine site of the GABAA receptor.
Pipequaline (INN) is an anxiolytic drug that was never marketed. It possesses a novel chemical structure that is not closely related to other drugs of this type. The drug has a similar pharmacological profile to the benzodiazepine family of drugs, but with mainly anxiolytic properties and very little sedative, amnestic or anticonvulsant effects, and so is classified as a nonbenzodiazepine anxiolytic.
SL651498 is an anxiolytic and anticonvulsant drug used in scientific research, with a chemical structure most closely related to β-carboline derivatives such as abecarnil and gedocarnil. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.
CL-218,872 is a sedative and hypnotic drug used in scientific research. It has similar effects to sedative-hypnotic benzodiazepine drugs such as triazolam, but is structurally distinct and so is classed as a nonbenzodiazepine hypnotic.
Y-23684 is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.
CGS-20625 is an anxiolytic drug used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. It produces anxiolytic and anticonvulsant effects, but with no sedative effects even at high doses, and no significant muscle relaxant effects. It is orally active in humans, but with relatively low bioavailability.
ELB-139 (LS-191,811) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.
NS-2664 (LS-193,048) is an anxiolytic drug with a novel chemical structure, developed by the small pharmaceutical company NeuroSearch. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. NS-2664 is a potent but non-selective partial agonist at GABAA receptors, although with little efficacy at the α1 subtype and more at α2 and α3. It has potent anticonvulsant effects in animal studies, but a relatively short duration of action, and produces little sedative effects or physical dependence.
NS-2710 (LS-193,970) is an anxiolytic drug with a novel chemical structure, developed by the small pharmaceutical company NeuroSearch. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. NS-2710 is a potent but non-selective partial agonist at GABAA receptors, although with little efficacy at the α1 subtype and more at α2 and α3. It has anxiolytic effects comparable to chlordiazepoxide, and while it is a less potent anticonvulsant than the related drug NS-2664, it has a much longer duration of action, and similarly to other α2/α3-preferring partial agonists produces little sedative effects or physical dependence.
TPA-023 (MK-0777) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. It is a subtype-selective, mixed allosteric modular at the benzodiazepine location on GABAA receptors, where it acts as a partial agonist at the α2 and α3 subtypes, but as a silent antagonist at α1 and α5 subtypes. It has primarily anxiolytic and anticonvulsant effects in animal tests, but with no sedative effects even at 50 times the effective anxiolytic dose.
TP-13 is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. It is a subtype-selective partial agonist at GABAA receptors, binding selectively to GABAA receptor complexes bearing α2 and α3 subunits. It has modest anticonvulsant activity although less than that of diazepam, and its main effect is likely to be selective anxiolytic action, as seen with other related α2/3-preferring agonists such as L-838,417.
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.
ZK-93423 is an anxiolytic drug from the β-Carboline family, closely related to abecarnil. It is a nonbenzodiazepine GABAA agonist which is not subtype selective and stimulates α1, α2, α3, and α5-subunit containing GABAA receptors equally. It has anticonvulsant, muscle relaxant and appetite stimulating properties comparable to benzodiazepine drugs. ZK-93423 has also been used as a base to develop new and improved beta-carboline derivatives and help map the binding site of the GABAA receptor.
FG-8205 (L-663,581) is an imidazobenzodiazepine derivative related to bretazenil, which acts as a partial agonist at GABAA receptors, with slight selectivity for the α1-containing subtype. In animal tests it has anxiolytic and anticonvulsant effects but with little sedation or ataxia produced.
Imepitoin (INN), sold under the brand name Pexion, is an anticonvulsant which is used in veterinary medicine in Europe to treat epilepsy in dogs. It was recently approved in the United States. The drug also has anxiolytic effects. It was originally developed to treat epilepsy in humans, but clinical trials were terminated upon findings of unfavorable metabolic differences in smokers and non-smokers.
