GABAA receptor negative allosteric modulators

RDX (Research Department Explosive or Royal Demolition Explosive), or hexogen, also known by other names, is an organic compound with the formula (CH2N2O2)3. It is white, odorless, tasteless, and widely used as an explosive. Chemically, it is classified as a nitroamine alongside HMX, which is a more energetic explosive than trinitrotoluene (TNT). It was used widely in World War II and remains common in military applications. It is lower performing and more toxic than modern replacements like TKX-50.

Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken by mouth, as eye drops, as ear drops, or intravenously.

Furosemide, sold under the brand name Lasix among others, is a loop diuretic medication used to treat edema due to heart failure, liver scarring, or kidney disease. Furosemide may also be used for the treatment of high blood pressure. It can be taken intravenously or orally. When given intravenously, furosemide typically takes effect within five minutes; when taken orally, it typically metabolizes within an hour.

Naloxone, sold under the brand name Narcan among others, is an opioid antagonist, a medication used to reverse or reduce the effects of opioids. For example, it is used to restore breathing after an opioid overdose. Effects begin within two minutes when given intravenously, five minutes when injected into a muscle, and ten minutes as a nasal spray. Naloxone blocks the effects of opioids for 30 to 90 minutes.

Levofloxacin, sold under the brand name Levaquin among others, is a broad-spectrum antibiotic of the fluoroquinolone drug class. It is the left-handed isomer of the medication ofloxacin. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori (in combination with other medications), urinary tract infections, Legionnaires' disease, chronic bacterial prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. It is available by mouth, intraveno

Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, H. pylori infection, and Lyme disease. Clarithromycin can be taken by mouth as a tablet or liquid or can be infused intravenously.

Lindane, also known as '''gamma-hexachlorocyclohexane (γ-HCH), gammaxene, Gammallin and benzene hexachloride (BHC'''), is an organochlorine chemical and an isomer of hexachlorocyclohexane that has been used both as an agricultural insecticide and as a pharmaceutical treatment for lice and scabies.

Thujone () is a ketone and a monoterpene that occurs predominantly in two diastereomeric (epimeric) forms: (−)-α-thujone and (+)-β-thujone.

Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functions as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids both in the gonads and in various other tissues. However, DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid and modulator of neurotrophic factor recep

Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken by mouth or injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prostatitis, plague, and certain types of infectious diarrhea. Other uses, along with other medications, include treating multidrug resistant tuberculosis. An eye drop may be used for a superficial bacterial infection of the eye and an ear drop may be used for otitis media when a hole in the ear drum is present.

Dieldrin is an organochlorine compound originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the insect to form dieldrin which is the active compound. Both dieldrin and aldrin are named after the Diels–Alder reaction which is used to form aldrin from a mixture of norbornadiene and hexachlorocyclopentadiene.

thumb|A vial of flumazenil solution for injection

Fipronil is a broad-spectrum insecticide that belongs to the phenylpyrazole insecticide class. Fipronil disrupts the insect central nervous system by blocking the ligand-gated ion channel of the GABAA receptor (IRAC group 2B) and glutamate-gated chloride (GluCl) channels. This causes hyperexcitation of contaminated insects' nerves and muscles. Fipronil's specificity towards insects is believed to be due to its greater binding affinity for the GABAA receptors of insects than to those of mammals, and for its action on GluCl channels, which do not exist in mammals. , there does not appear to be s

Imipenem, sold under the brand name Primaxin among others, is a synthetic β-lactam antibiotic belonging to the carbapenems chemical class. developed by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus playing a key role in the treatment of infections not readily treated with other antibiotics. It is usually administered through intravenous injection.

injectible form of birth control

Cicutoxin is a naturally-occurring poisonous chemical compound produced by several plants from the family Apiaceae including water hemlock (Cicuta species) and water dropwort (Oenanthe crocata). The compound contains polyene, polyyne, and alcohol functional groups and is a structural isomer of oenanthotoxin (also found in water dropwort) and bupleurotoxin (found in Bupleurum longiradiatum). All of these belong to the C17-polyacetylenes chemical class.

Nicardipine (Cardene) is a medication used to treat angina and hypertension, especially for hemorrhagic stroke patients. It belongs to the dihydropyridine class of calcium channel blockers (CCBs). It is also used for Raynaud's phenomenon. It is available in by mouth and intravenous formulations. It has been used in percutaneous coronary intervention.

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.

Picrotoxin, also known as cocculin, is a poisonous crystalline plant compound. It was first isolated by the French pharmacist and chemist Pierre François Guillaume Boullay (1777–1869) in 1812. The name "picrotoxin" is a combination of the Greek words "picros" (bitter) and "toxicon" (poison). A mixture of two different compounds, picrotoxin occurs naturally in the fruit of the Anamirta cocculus plant, although it can also be synthesized chemically.

Pentylenetetrazol (PTZ), also known as pentylenetetrazole, pentetrazol (INN), and pentamethylenetetrazol, is a drug formerly used as a circulatory and respiratory stimulant. High doses cause convulsions, as discovered by Hungarian-American neurologist and psychiatrist Ladislas J. Meduna in 1934. It has been used in convulsive therapy, and was found to be effective in treating depression, but side effects, such as uncontrolled seizures, were difficult to avoid. In 1939, pentylenetetrazol was replaced by electroconvulsive therapy, which is easier to administer, as the preferred method for induci

Anisatin is an extremely toxic, insecticidally active component of the shikimi plant. The lethal dose is 1 mg/kg (i.p.) in mice. Symptoms begin to appear about 1–6 hours after ingestion, beginning with gastrointestinal ailments, such as diarrhea, vomiting, and stomach pain, followed by nervous system excitation, seizures, loss of consciousness, and respiratory paralysis, which is the ultimate cause of death.

Cyclothiazide (Anhydron, Acquirel, Doburil, Fluidil, Renazide, Tensodiural, Valmiran), sometimes abbreviated CTZ, is a benzothiadiazide (thiazide) diuretic and antihypertensive that was originally introduced in the United States in 1963 by Eli Lilly and was subsequently also marketed in Europe and Japan. Related drugs include diazoxide, hydrochlorothiazide, and chlorothiazide.

chemical compound

Oenanthotoxin is a toxin extracted from hemlock water-dropwort (Oenanthe crocata) and other plants of the genus Oenanthe. It is a central nervous system poison, and acts as a noncompetitive antagonist of the neurotransmitter gamma-aminobutyric acid. A case has been made for the presence of this toxin in local Oenanthe species playing a causative role in euthanasia in ancient Sardinia. It was crystallized in 1949 by Clarke and co-workers. It is structurally closely related to the toxins cicutoxin and carotatoxin. Oenanthotoxin is a C17 polyacetylene isomer of cicutoxin.

Bilobalide is a biologically active terpenic trilactone present in Ginkgo biloba.

Tetramethylenedisulfotetramine (TETS) is an organic compound used as a rodenticide (rat poison). It is an odorless, tasteless white powder that is slightly soluble in water, DMSO and acetone, and insoluble in methanol and ethanol. It is a sulfamide derivative. It can be synthesized by reacting sulfamide with formaldehyde solution in acidified water. When crystallized from acetone, it forms cubic crystals with a melting point of 255–260 °C.

Bemegride, sold under the brand name Megimide among others, is a central nervous system (CNS) stimulant first manufactured in 1911, and which has been used in hypnotic overdose.

chemical compound

Flurothyl (formerly under the trade name Indoklon) (IUPAC names: 1,1,1-trifluoro-2-(2,2,2-trifluoroethoxy)ethane or bis(2,2,2-trifluoroethyl) ether) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether and sevoflurane, but having the opposite effects, acting as a stimulant and convulsant. A clear and stable liquid, it has a mild ethereal odor whose vapors are non-flammable. It is excreted from the body by the lungs in an unchanged state.

Amentoflavone is a biflavonoid (bis-apigenin coupled at 8 and 3 positions, or 3,8-biapigenin) constituent of a number of plants including Ginkgo biloba, Chamaecyparis obtusa (hinoki), Biophytum sensitivum, Selaginella tamariscina, Hypericum perforatum (St. John's Wort) and Xerophyta plicata.

Morphine-3-glucuronide is a metabolite of morphine produced by UGT2B7. It is not active as an opioid agonist, but does have some action as a convulsant, which does not appear to be mediated through opioid receptors, but rather through interaction with glycine and/or GABA receptors. As a polar compound, it has a limited ability to cross the blood–brain barrier, but kidney failure may lead to its accumulation and result in seizures. Probenecid and inhibitors of P-glycoprotein can enhance uptake of morphine-3-glucuronide and, to a lesser extent, morphine-6-glucuronide. Reported side effects relat

Apalutamide, sold under the brand name Erleada among others, is a nonsteroidal antiandrogen (NSAA) medication used for the treatment of prostate cancer. It is an androgen receptor inhibitor. It is taken by mouth.

Laudanosine or '''N-methyltetrahydropapaverine''' is a metabolite of the pharmaceutical drugs atracurium and cisatracurium. Laudanosine decreases the seizure threshold, and thus it can induce seizures if present at sufficient threshold concentrations; however, such concentrations are unlikely to be produced consequent to chemodegradable metabolism of clinically administered doses of cisatracurium or atracurium.

ZK-93426 (ethyl-5-isopropoxy-4-methyl-β-carboline-3-carboxylate) is a drug from the β-carboline family. It acts as a weak partial inverse agonist of benzodiazepine receptors, meaning that it causes the opposite effects to the benzodiazepine class of drugs and has anxiogenic properties, although unlike most benzodiazepine antagonists it is not a convulsant and actually has weak anticonvulsant effects. In human tests it produced alertness, restlessness and feelings of apprehension, and reversed the effect of the benzodiazepine lormetazepam. It was also shown to produce nootropic effects and incr

Phenylsilatrane is a convulsant chemical which has been used as a rodenticide. Phenylsilatrane and some of its analogs with 4-substituents of H, CH3, Cl, Br, and CSi(CH3)3 are highly toxic to mice. They have been observed in the laboratory to inhibit the 35S-tert-butylbicyclophosphorothionate (TBPS) binding site (GABA-gated chloride channel) of mouse brain membranes.

Suritozole (MDL 26,479) is an investigational cognition enhancer. It acts as a partial inverse agonist at the benzodiazepine receptor site on the GABAA ion channel complex, but does not have either anxiogenic or convulsant effects, unlike other BZD inverse agonists such as DMCM. It was investigated for the treatment of depression and Alzheimer's disease in the 90s, but clinical development seems to have been discontinued.

chemical compound

DMCM (methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) is a drug from the β-carboline family that induces anxiety and convulsions by acting as a negative allosteric modulator of GABAA receptors — functionally opposite to benzodiazepines and related drugs which are positive allosteric modulators — and is used in scientific research for these properties to test new anxiolytic and anticonvulsant medications, respectively. It has also been shown to produce analgesic effects in animals, which is thought to be the drug's induced panic reducing the perception of pain.

Iomazenil (also known as Ro16-0154, INN, USAN; benzodine) is an antagonist and partial inverse agonist of benzodiazepine and a potential treatment for alcohol use disorder. The compound was introduced in 1989 by pharmaceutical company Hoffmann-La Roche as an Iodine-123-labelled SPECT tracer for imaging benzodiazepine receptors (GABAA receptors) in the brain. Iomazenil is an analogue of flumazenil (Ro15-1788).

FG-7142 (ZK-31906) is a drug of the β-carboline family which acts as a partial inverse agonist at the benzodiazepine allosteric site of the GABAA receptor. It has anorectic, anxiogenic and pro-convulsant effects. It also increases release of acetylcholine and noradrenaline, and improves memory retention in animal studies.

chemical compound

Fluralaner (INN), sold under the brand name Bravecto among others, is a systemic insecticide and acaricide that is administered orally or topically.

Sarmazenil (Ro15-3505) is a drug from the benzodiazepine family. It acts as a partial inverse agonist of benzodiazepine receptors, meaning that it causes the opposite effects to most benzodiazepine drugs, and instead acts as an anxiogenic and convulsant. It is used in veterinary medicine to reverse the effects of benzodiazepine sedative drugs in order to rapidly re-awaken anesthetized animals.

Ro15-4513 is a weak partial inverse agonist of the benzodiazepine class of drugs, developed by Hoffmann–La Roche in the 1980s. It acts as an inverse agonist (which acts in a similar way as a competitive antagonist). The drug has been explored as possible antidote to the sedative and cognitively impairing effects of ethanol.

L-655,708 (FG-8094) is a nootropic drug invented in 1996 by a team working for Merck, Sharp and Dohme, that was the first compound developed which acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor. It acts as an inverse agonist at the α1, α2, α3 and α5 subtypes, but with much higher affinity for α5, and unlike newer α5 inverse agonists such as α5IA, L-655,708 exerts its subtype selectivity purely via higher binding affinity for this receptor subtype, with its efficacy as an inverse agonist being around the same at all the sub

Prasterone, also known as dehydroepiandrosterone (DHEA) and sold under the brand name Intrarosa among others, is a medication as well as over-the-counter dietary supplement which is used to correct DHEA deficiency due to adrenal insufficiency or old age, as a component of menopausal hormone therapy, to treat painful sexual intercourse due to vaginal atrophy, and to prepare the cervix for childbirth, among other uses. It is taken by mouth, by application to the skin, in through the vagina, or by injection into muscle.

PWZ-029 is a benzodiazepine derivative drug with nootropic effects developed by WiSys, It acts as a subtype-selective, mixed agonist-inverse agonist at the benzodiazepine binding site on the GABAA receptor, acting as a partial inverse agonist at the α5 subtype and a weak partial agonist at the α3 subtype. This gives it a mixed pharmacological profile, producing at low doses memory-enhancing effects but with no convulsant or anxiogenic effects or muscle weakness, although at higher doses it produces some sedative effects.