Imidazenil is an experimental

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 ...

drug which is derived from the

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 ...

family, and is most closely related to other imidazobenzodiazepines such as

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia, premedication before surgical anesthesia, and procedural sedation, and to treat psychomotor agitation, severe agitation. It induces ...

flumazenil Flumazenil, also known as flumazepil, is a selective GABAA receptor, GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines (partic ...

, and bretazenil. Imidazenil is a highly potent

benzodiazepine receptor The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous Ligand (biochemistry), ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Accurate regul ...

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 ...

with an unusual profile of effects, producing some of the effects associated with normal benzodiazepines such as

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 ...

and

effects, yet without any notable

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

or amnestic effects. In fact, imidazenil blocks the sedative effects of

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

, yet without lowering the convulsion threshold, and so potentially could be a more flexible antidote than the antagonist

which is commonly used to treat benzodiazepine overdose at present. Imidazenil has not yet been developed commercially for use in humans, however it has been suggested as a safe and effective treatment for

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

, a potent yet non-sedating anticonvulsant which might be particularly useful in the treatment of poisoning with

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemistry, organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (ACh ...

s, and as a novel treatment for

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

. In rats, imidazenil has been demonstrated to have low tolerance or dependence liability, unlike other benzodiazepine receptor agonist ligands, such as diazepam, bretazenil.

Pharmacodynamics

Imidazenil is selective over the type of

GABAA receptor The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous Ligand (biochemistry), ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Accurate regul ...

it acts on. It acts as a partial agonist on those with a α₁β₂γ_2S composition and as a full agonist on those with a α₅β₂γ_2S composition. Its action can be compared to that of

clobazam Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxiosele ...

, another anxioselective benzodiazepine. Clobazam's active metablite ''N''-desmethylclobazam has lower affinity on receptors with an α₁ subunit compared to those with an α₂. It is believed that the subjective, ataxic, and sedative properties are mediated via α₁-containing receptors, while the anxiolytic effects are mediated via the ones with α₂, α₃, or α₅.

References

{{GABAAR PAMs Carboxamides 2-Bromophenyl compounds Fluoroarenes GABAA receptor positive allosteric modulators Imidazobenzodiazepines

Pharmacodynamics

See also

References