Nonbenzodiazepines /ˌnənbɛnzɵdaɪˈæzɨpiːn/ (sometimes referred to colloquially as "Z-drug") are a class of psychoactive drugs that are very benzodiazepine-like in nature. Nonbenzodiazepines pharmacodynamics are almost entirely the same as benzodiazepine drugs and therefore employ similar benefits, side-effects, and risks. Nonbenzodiazepines, however, have dissimilar or entirely different chemical structures and, therefore, are unrelated to benzodiazepines on a molecular level. Classes Core structures of selected nonbenzodiazepines (left three diagrams) and the structure of benzodiazepine (right) for comparison. Nonbenzodiazepine
Pyrazolopyrimidine is a heterocyclic chemical compound with the molecular formula C6H5N3. It forms the central core of a variety of more complex chemical compounds including some pharmaceuticals and pesticides. 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. Panadiplon acts as a high-affinity GABAA receptor partial agonist, 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. Panadiplon however continues to be used in animal research, mainly as a subtype-selective reference drug to compare other GABAA agonists against. Jump up ^ 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. Mechanism of action
Indiplon Indiplon (INN and USAN) is a nonbenzodiazepine, hypnotic sedative that was developed in 2 formulations - an immediate release product for sleep onset and a modified-release (a.k.a. controlled-release or extended-release) version for sleep maintenance. 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, Starnoc and Andante) is a sedative-hypnotic, almost entirely used for the management/treatment of insomnia. It is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class. Sonata (US) is manufactured by King Pharmaceuticals of Bristol, TN. Gedeon Richter Plc. manufactures zaleplon under the brand name Andante. Starnoc has been discontinued in Canada.
β-Carboline (9H-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. 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 GABAA receptor. 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
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. See also References ZK-93423
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. Cyclopyrroloneseszopiclone - hypnotic (Lunesta)zopiclone - hypnotic (Imovane)pagoclone - anxiolyticsuriclone - anxiolyticpazinaclone - anxiolyticsuproclone - anxiolyticBritish Medical Journal
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, 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 GABAA receptors, although suriclone is more subtype-selective than most benzodiazepines. Jump up ^ 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. 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 (resulting in an increased response to endogenous GABA), in a similar manner to other drugs of this class. Jump up ^ Psychotropics.dk.
Eszopiclone, marketed by Sunovion 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 (Lunesta) along with other "Z-drugs" including zolpidem (Ambien), zaleplon (Sonata) are the most commonly prescribed sedative hypnotics in the US. Eszopiclone is not marketed in the European Union following a 2009 decision by the EMA denying it new active substance status, in which it ruled that eszopiclone was too similar to zopiclone to be considered a new patentable product. Eszopiclone
Zopiclone (brand name Imovane in Canada, Australia, Sweden, Finland, Norway, Russia and the United Kingdom, brand name Zimovane in Europe) is a nonbenzodiazepine 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 was synthesized by a French team working for Rhone-Poulenc & Rorer S.A. 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. David Nutt from the University of Bristol has suggested pagoclone as a possible base from which to make a better social drug, as it produces the positive effects of alcohol, such as relaxation and sociability, but without also causing the negative effects like aggression, amnesia, nausea, loss of coordination and liver damage. Its effect can be quickly reversed by the action of flumazenil, which is already used as an antidote to benzodiazepine overdose. Dr. Pagoclone