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Structures of benzodiazepine recognition site ligands
Published in Adam Doble, Ian L Martin, David Nutt, Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
Adam Doble, Ian L Martin, David Nutt
The first compound of this series to be synthesised and described was zopiclone, which displayed an IC50 of about 30 nM versus [H]-diazepam in rat cortex (Blanchard et al, 1979). Later, more potent cyclopyrrolone compounds, including suriclone (Blanchard et al, 1983), suproclone (Garret et al, 1984), RP 59037 (Doble et al, 1993) and DN 2327 (Wada and Fukuda, 1991) were synthesised. Figure 5.6 shows the chemical structures of zopiclone, suriclone and suproclone. It is clear from structure-activity studies within this series that the methyl-4 piperazinyl carbonyl group is essential to activity, while a chlorine group in the para position of the pyridine ring results in an increase of activity and a decrease of toxicity. Other substituents, -CN, -OCH3 or -NO2, at this position do not improve activity. The ring fused in the isoindolic moiety can be benzene (RP 25519) or a heterocyclic ring (zopiclone). Suriclone, which exhibits high affinity, is characterised by a heterocyclic ring fused in the isoindolic moiety and by a bicyclic substituent at the isoindole nitrogen.
Olfaction in Palliative Care Patients
Published in Victor R. Preedy, Handbook of Nutrition and Diet in Palliative Care, 2019
Sagit Shushan, Arkadi Yakirevitch
Drugs in many major pharmacological categories (dopaminergic antagonists, gamma-aminobutyric acid [GABA]-ergic agonists, calcium channel blockers and some orally active local anaesthetic, antiarrhythmic drugs) can impair olfactory function (Henkin 1994) and do so more commonly than presently appreciated. Table 17.3 shows some medications that were reported to alter smell and/or taste. Impairment usually affects sensory function at a molecular level by drug inactivation of receptor function through inhibition of tastant/odorant receptor, causing two major perceptual modifications: decreased perception (i.e., hyposmia or anosmia) and/or perception distortion (i.e., dysosmia) (Table 17.1). Those modifications can impair appetite and food intake, trigger significant lifestyle changes and may even require discontinuation of drug administration. Some sleep-inducing agents are associated with taste and, in rare instances, smell disturbances as potential adverse effects. Zolpidem is listed in the Physicians’ Desk Reference as producing “taste perversion” and, more infrequently, “parosmia” (Physicians’ Desk Reference 2005). Eszopiclone, a nonbenzodiazepine pyrrolopyrazine derivative of the cyclopyrrolone class, is associated with complaints of “unpleasant taste” (Krystal et al. 2003).
A primer on sleeping, dreaming, and psychoactive agents
Published in Journal of Social Work Practice in the Addictions, 2023
Cyclopyrrolones, otherwise known as Z-drugs, while pharmacologically distinct from benzodiazepines, still bind to GABA receptors. The most prominent feature of Z-drugs is that they decrease sleep latency and increase the duration of sleep. The duration of stage one sleep is shortened, while the time spent in stage two sleep is typically increased. In most studies, stage three sleep tended to be increased, but no change and actual decreases was observed in clinical trials. The effect of zopiclone on stage three sleep differed from that of traditional benzodiazepines, which suppress slow-wave sleep. While the onset of REM sleep was delayed, this drug group does not appear to reduce the total duration of REM sleep, according to pharmaceutical agency sponsored studies (Nu-Pharm, 2009; Sanofi-Aventis, 2018). However, in 2014 Health Canada placed a recommended dosage limitation on the use of zopiclone due to the adverse behaviors its users were experiencing, including impairments lasting for up to two days. Amnesia can result from using this drug, as highlighted by reports of people getting out of bed, while not fully awake after taking cyclopyrrolones and unknowingly engaging in activities, with no memory of the action the next day (Sanofi-Aventis, 2018).
Clinical characteristics and outcomes associated with bupropion overdose: a Canadian perspective
Published in Clinical Toxicology, 2020
Emily Stewart, Keerat Grewal, Heather Hudson, Margaret Thompson, Jesse Godwin
For the secondary objective of this study we were interested in determining predictors of seizure after a bupropion overdose. The main exposure variable was benzodiazepine co-ingestion at the time of the bupropion overdose. Zopiclone, a hypnotic cyclopyrrolone, was considered a benzodiazepine because it has a mechanism of action that is similar to benzodiazepines. Zolpidem, a nonbenzodiazepine GABA agonist that acts a sedative and hypnotic, was not a coingestant in any case.