The nonbenzodiazepines , also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines , with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures. [ 1 ] [ 2 ] [ edit ] Classes Core structures of selected nonbenzodiazepines (left three diagrams) and the structure of benzodiazepine (right) for comparison. Currently, the major chemical classes of nonbenzodiazepines are: Imidazopyridines Nonbenzodiazepine
Pyrazolopyrimidine is a heterocyclic chemical compound with the molecular formula C 6 H 5 N 3 . It forms the central core of a variety of more complex chemical compounds including some pharmaceuticals and pesticides. [ edit ] Pharmaceuticals The pyrazolopyrimidines are a class of sedative and anxiolytic drugs related (in terms of their effect) to benzodiazepines . Most of the drugs from this class marketed to date are intended to induce sleep , and are prescribed for people suffering insomnia , however some newer compounds produce anxiolytic effects with relatively little sedation, and are being developed for use as non-sedating anti-anxiety drugs. They include: Pyrazolopyrimidine
Panadiplon (U-78875) is an anxiolytic drug with a novel chemical structure that is not closely related to other drugs of this type. It has a similar pharmacological profile to the benzodiazepine family of drugs, but with mainly anxiolytic properties and relatively little sedative or amnestic effect, and so is classified as a nonbenzodiazepine anxiolytic. [ 1 ] Panadiplon acts as a high-affinity GABA A receptor partial agonist , [ 2 ] [ 3 ] but despite showing a useful effects profile of a potent anxiolytic with little sedative effects, panadiplon was discontinued from clinical development for use in humans after showing evidence of liver damage in both animals and human trials. [ 4 ] [ 5 ] Panadiplon however continues to be used in animal research, mainly as a subtype-selective reference drug to compare other GABA A agonists against. [ 6 ] [ 7 ] ^ Tang AH, Franklin SR, Himes CS, Ho PM. Panadiplon
Ocinaplon Ocinaplon is an anxiolytic drug in the pyrazolopyrimidine family of drugs. Other pyrazolopyrimidine drugs include zaleplon and indiplon . Ocinaplon has a similar pharmacological profile to the benzodiazepine family of drugs, but with mainly anxiolytic properties and relatively little sedative or amnestic effect. [ 1 ] [ edit ] Mechanism of action
Indiplon Indiplon ( INN and USAN ) is a nonbenzodiazepine , hypnotic sedative was developed in 2 formulations - an immediate release product for sleep onset and a modified-release version for sleep maintenance. [ edit ] Mode of action Indiplon works by enhancing the action of the inhibitory neurotransmitter GABA , like most other nonbenzodiazepine sedatives.
Zaleplon Zaleplon (marketed under the brand names Sonata and Starnoc ) is a sedative / hypnotic , almost entirely used for the management/treatment of insomnia . It is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class. [ 1 ] Sonata (US) is manufactured by King Pharmaceuticals of Bristol, TN ; Starnoc has been discontinued in Canada . It's prescribed rarely in the United Kingdom ; with zopiclone Imovane being the preferred "Z-Drug" by the National Health Service (NHS), as zaleplon has been discontinued by the NHS . [ edit ] Medical uses
β- Carboline (9 H - pyrido [3,4- b ] indole ) also known as norharmane is a nitrogen containing heterocycle . It is also the prototype of a class of compounds known as β-carbolines. [ edit ] Pharmacology β-Carboline alkaloids are widespread in plants and animals , and frequently act as benzodiazepine inverse agonists. beta-Carboline
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 GABA A receptor . [ 1 ] [ 2 ] Abecarnil was originally developed as an anti-anxiety drug, but has not as yet been commercially developed for use in humans, instead so far mainly being used for research into the development of other new sedative and anxiolytic drugs. Abecarnil
Cyclopyrrolones Cyclopyrrolones are a family of hypnotic and anxiolytic nonbenzodiazepine drugs with similar pharmacological profiles to the benzodiazepine derivatives. Although cyclopyrrolones are chemically unrelated to benzodiazepines, they function via the benzodiazepine receptor/ GABA neurotransmitter . The best known cyclopyrrolone derivatives are zopiclone (Imovane) and its enantiomer eszopiclone (Lunesta), which are used to treat insomnia , and have a known potential for abuse. Other cyclopyrrolone derivatives include suriclone , pagoclone , pazinaclone and suproclone . Cyclopyrrolones eszopiclone - hypnotic (Lunesta) zopiclone - hypnotic (Imovane) pagoclone - anxiolytic suriclone - anxiolytic pazinaclone - anxiolytic suproclone - anxiolytic
Suriclone ( Suril ) is a sedative and anxiolytic drug in the cyclopyrrolone family of drugs. Other cyclopyrrolone drugs include zopiclone and pagoclone . Suriclone has a very similar pharmacological profile to the benzodiazepine family of drugs including sedative and anxiolytic properties but with less amnestic effects, [ 1 ] [ 2 ] and its chemical structure is quite different from that of the benzodiazepine drugs. The mechanism of action by which suriclone produces its sedative and anxiolytic effects is by modulating GABA A receptors , although suriclone is more subtype-selective than most benzodiazepines. [ 3 ] ^ Gilburt SJ, Fairweather DB, Kerr JS, Hindmarch I. Suriclone
Suproclone Suproclone is a sedative and anxiolytic drug in the cyclopyrrolone family of drugs, developed by the French pharmaceutical company Rhône-Poulenc. [ 1 ] Other cyclopyrrolone drugs include zopiclone , pagoclone and suriclone . Suproclone is very similar in structure to the related drug suriclone , but little information has been published about it specifically. However it can be expected that the mechanism of action by which suproclone produces its sedative and anxiolytic effects is by modulating benzodiazepine receptors, in a similar manner to other drugs of this class. [ 2 ] [ 3 ] ^ Psychotropics.dk.
Eszopiclone , marketed by Sepracor under the brand-name Lunesta , is a nonbenzodiazepine hypnotic which is slightly effective for insomnia . Eszopiclone is the active dextrorotatory stereoisomer of zopiclone , and belongs to the class of drugs known as cyclopyrrolones . Eszopiclone is a short acting nonbenzodiazepine sedative hypnotic. Eszopiclone
Zopiclone (brand name Imovane in Canada and Australia, brand name Zimovane in Europe). is a non-benzodiazepine hypnotic agent used in the treatment of insomnia . It is a cyclopyrrolone , which increases the normal transmission of the signal substance GABA in the central nervous system, as benzodiazepines do, but in a different way. As zopiclone is sedating it is marketed as a sleeping pill. Zopiclone
Pagoclone is an anxiolytic drug from the cyclopyrrolone family, related to better-known drugs such as the sleeping medication zopiclone . 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 . Pagoclone was originally developed as an anti-anxiety drug, but never commercialised. It is a partial agonist acting at GABA A receptors in the brain. In contrast to zopiclone, pagoclone produces anxiolytic effects with little or no sedative or amnestic actions at low doses. [ 1 ] This is because pagoclone is a subtype-selective drug which binds primarily to the α2/α3 subtypes of the GABA A receptor which are responsible for the anti-anxiety effects of these kind of drugs, but has relatively little efficacy at the α1 subtype which produces the sedative and memory loss effects. [ 2 ] Pagoclone
Pazinaclone ( DN-2327 ) is a sedative and anxiolytic drug in the cyclopyrrolone family of drugs. Other cyclopyrrolone drugs include zopiclone and eszopiclone . Pazinaclone has a very similar pharmacological profile to the benzodiazepine family of drugs including sedative and anxiolytic properties, but with less amnestic effects, [ 1 ] and at low doses it is a relatively selective anxiolytic, with sedative effects only appearing at higher doses. [ 2 ] Pazinaclone produces its sedative and anxiolytic effects by acting as a partial agonist at GABA A benzodiazepine receptors, although pazinaclone is more subtype-selective than most benzodiazepines. [ 3 ] Pazinaclone