BDZs, designer BDZs, and Z-drugs: pharmacology and misuse insights

2021 ◽  
Vol 27 ◽  
Author(s):  
Simona Zaami ◽  
Silvia Graziano ◽  
Roberta Tittarelli ◽  
Renata Beck ◽  
Enrico Marinelli

: Benzodiazepines (BZDs) are a widely prescribed class of sedative-hypnotics compounds for the treatment of a broad range of conditions as anxiety and obsessive-compulsive disorders, phobias, sleep related problems associated with insomnia and for the management of alcohol and GHB withdrawal. Zolpidem, zopiclone and zaleplon, commonly known as Z-drugs are non-benzodiazepine hypnotic drug with pharmacology similar to BDZs. Despite their usefulness, BDZs and Z-drugs present a potential for abuse and dependence. Moreover, the non-medical use of BDZs is a well-known phenomenon and represents an increasingly widespread public health problem since is associated with an elevated risk of serious health consequences or fatal overdose, especially among specific group of users. The spectrum of BDZs and Z-drugs misuse is extended by new synthetic BDZs, which may pose high risks to users, since the majority have never undergone clinical trials or tests and consequently their pharmacology and toxicology is largely unknown.

2019 ◽  
Author(s):  
German I. Todorov ◽  
Karthikeyan Mayilvahanan ◽  
David Ashurov ◽  
Catarina Cunha

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is raising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behavior and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently lead to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about possible mechanism involved in OCD and ASD. Additionally, it shows that modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of high inherited risk of certain mental health conditions.


2016 ◽  
Vol 4 (2) ◽  
pp. 103-111
Author(s):  
María Yoldi-Negrete ◽  
Mónica Flores-Ramos ◽  
Alejandra Montserrat Rodríguez-Ramírez ◽  
Carvajal-Lohr Armando ◽  
Jorge Ávila-Solorio ◽  
...  

2014 ◽  
Vol 29 (S3) ◽  
pp. 546-546
Author(s):  
N. Benzina ◽  
S.L. Mondragon ◽  
N. Ouarti ◽  
L. Mallet ◽  
E. Burguiere

Behavioral flexibility is the ability of a subject to change its behavior according to contextual cues. In humans, Obsessive Compulsive Disorders (OCD) is characterized by repetitive behavior, performed through rigid rituals. This phenomenological observation has led to explore the idea that OCD patients may have diminished behavioral flexibility. To address this question we developed innovative translational approaches across multiple species, including human patients suffering from obsessive-compulsive disorders, and rodent genetic models of OCD to provide original data in the perspective of enlightening the neurocognitive bases of compulsive behaviors. Behavioral flexibility may be challenged in experimental tasks such as reversal learning paradigms. In these tasks, the subject has to respond to either of two different visual stimuli but only one stimulus is positively rewarded while the other is not. After this first association has been learned, reward contingency are inverted, so that the previously neutral stimulus is now rewarded, while the previously rewarded stimulus is not. Performance in reversal learning is indexed by the number of perseverative errors committed when participants maintain their response towards previously reinforced stimulus in spite of negative reward. Unsurprisingly, this behavioral task has been adapted to mice using various response modalities (T-maze, lever press, nose-poke). Using animal models of compulsive behaviors give much more possibilities to study the deficient functions and their underlying neural basis that could lead to pathological repetitive behaviors. Here we present new behavioral set-ups that we developed in parallel in human (i.e. healthy subjects and OCD patients) and mice (i.e. controls and SAPAP3-KO mice) to study the role of the behavioral flexibility as a possible endophenotype of OCD. We observed that the subjects suffering of compulsive behaviors showed perseverative maladaptive behaviors in these tasks. By comparing the results of a similar task-design in humans and mouse models we will discuss the pertinence of such translational approach to further study the neurocognitive basis of compulsive behaviors.


2012 ◽  
Vol 27 ◽  
pp. 1
Author(s):  
V. Nejati ◽  
M. Safarzadeh ◽  
G. Maleki ◽  
A. Zabihzadeh ◽  
S.S. Aghaei Sabet

1996 ◽  
Vol 8 (1) ◽  
pp. 17-24
Author(s):  
W.M.A. Verhoeven ◽  
S. Tuinier ◽  
J.B.G.M. Noten

SummarySince the introduction of the monoamine oxydase inhibitors and the first tricyclic antidepressant (TCA) imipramine in the late fifties, the treatment of depressive disorders has been changed dramatically. Althought a great variety of antidepressants such as TCA's, selective serotoninte-re-uptake inhibitors (SSRI's) mianserin, trazodone, mirtazapine, moclobemide and venlafaxine has become available, the exact mode of action is not revealed as yet, and classification should be done according to the interference of antidepressants with central monoaminergic processes.As to the potential of causing interactions, special attention has to be given to the SSRI's because of their interference with the CYP450 isozyme system. Therapeutic monotoring is recommended for the TCA's. The choiseforan antidepressant should be based on various factors like symptomatology and severity of the depression, potential interactions and somatic and/or psychiatric comorbidity.Extensive clinical research has demonstrated that TCA's are the most effective for major depression with melancholia (vital depression) and depressive disorders in the elderly.


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