SL651498 is an

anxiolytic An anxiolytic (; also antipanic or anti-anxiety 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 ...

and

anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...

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 Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

drugs, but is structurally distinct and so is classed as a

nonbenzodiazepine Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive, depressant, sedative, hypnotic, anxiolytic drugs that are benzodiazepine-like in uses, such as f ...

anxiolytic. SL651498 is a subtype-selective GABA_A agonist, which acts as a

full agonist 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 agoni ...

at α₂ and α₃ subtypes, and as a

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

at α₁ and α₅ (although its action at α₅ subtypes is much weaker than at the others). In animal studies, it has primarily

effects, although some

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

and

muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeu ...

effects are observed at higher doses. It substitutes fully for the anxiolytic benzodiazepine

chlordiazepoxide Chlordiazepoxide hydrochloride, sold under the brand name Librium is a sedative and hypnotic medication of the benzodiazepine class. It is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol, benzodiazepines, and other drug ...

, but only partially substituted for the

imidazopyridine An imidazopyridine is a nitrogen containing heterocycle that is also a class of medication, drugs that contain this same chemical substructure. In general, they are GABAA receptor, GABAA receptor receptor_agonist, agonists, however recently proto ...

hypnotic drug

zolpidem Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and after beh ...

and the benzodiazepine

hypnotic A hypnotic (from Ancient Greek, Greek ''Hypnos'', sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to sleep induction, induce sleep and to trea ...

triazolam Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properti ...

. When given repeatedly it failed to produce tolerance or dependence, probably due to its low affinity and efficacy at the α₅ subtype. SL651498 has been suggested for development as a novel non-sedating anxiolytic drug for humans, although it is still only at an early stage of research. Preliminary human trials suggest similar efficacy to

lorazepam Lorazepam, sold under the brand name Ativan, Tavor among others, is a benzodiazepine medication. It is used to treat anxiety (including anxiety disorders), insomnia, severe agitation, active seizures including status epilepticus, alcoh ...

as an anxiolytic, but with little or no sedation or impairment of memory, motor skills or cognitive function. There are other possibly anxioselective compounds in development, such as

L-838,417 L-838,417 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. The compound was developed by Merck, Sharp and Dohme. ...

, NGD 91-3.

References

{{Tryptamines Anxiolytics Beta-Carbolines 1-Pyrrolidinyl compounds Fluoroarenes Lactams Carboxamides GABAA receptor positive allosteric modulators

See also

References