The discovery of chlordiazepoxide and the clinical introduction of benzodiazepines: Half a century of anxiolytic drugs

López-Muñoz, Francisco; Álamo, Cecilio; García-García, Pilar

doi:10.1016/j.janxdis.2011.01.002

Cited by 99 publications

(71 citation statements)

References 51 publications

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“…In addition, our present study shows that CDZ does not alter 5-HT and DA concentrations in the brain while inhibiting ALB, which confirms that the mode of action of this anxiolytic occurs independent of changes of bioamine levels in crayfish. In vertebrates, in spite of several reports having shown that benzodiazepine compounds can alter 5-HT or DA levels (Wise et al, 1972;Finlay et al, 1995), it is now accepted that CDZ acts as a GABA-A receptor agonist (Lopez-Munoz et al, 2011). Of course, our results in crayfish do not exclude the possibility that CDZ could alter stress response and bioamine levels in other conditions, i.e.…”

Section: Bioamine Levels After Anxiolytic Treatmentcontrasting

confidence: 79%

Serotonin, but not dopamine, controls stress response and anxiety-like behavior in crayfish, Procambarus clarkii.

Fossat

Bacqué-Cazenave

Deurwaerdère

et al. 2015

Journal of Experimental Biology

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In the animal kingdom, biogenic amines are widespread modulators of the nervous system that frequently interact to control mood. Our previous investigations in crayfish (Procambarus clarkii) have established that stress induces changes in brain serotonin (5-HT) concentrations that are responsible for the appearance of anxiety-like behavior (ALB). Here, we further analyze the roles of 5-HT and another biogenic amine, dopamine (DA), on the crayfish response to stress. We show that the intensity of crayfish ALB depends on the intensity of stressful stimulation and is associated with increased concentrations of 5-HT in the brain. These 5-HT levels were significantly correlated, before, as well as after stress, with those of DA, which were approximately 3-to 5-times less abundant. However, whereas the degree of ALB was clearly correlated with brain 5-HT concentrations, it was not significantly correlated with DA. Moreover, in contrast to injections of 5-HT, DA injections were not able to elicit a stress response or ALB. In addition, 5-HT and DA levels were not modified by treatment with the anxiolytic chlordiazepoxide, confirming that suppression of ALB by this GABA-A receptor ligand acts downstream and is independent of changes in crayfish bioamine levels. Our study also provides evidence that the anxiogenic effect of 5-HT injections can be prevented by a preliminary injection of 5-HT antagonists. Altogether, our results emphasize that the rises in brain concentrations of 5-HT, but not DA, play a role in controlling the induction and the intensity of crayfish ALB.

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Section: Bioamine Levels After Anxiolytic Treatmentcontrasting

confidence: 79%

Serotonin, but not dopamine, controls stress response and anxiety-like behavior in crayfish, Procambarus clarkii.

Fossat

Bacqué-Cazenave

Deurwaerdère

et al. 2015

Journal of Experimental Biology

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“…Little is known about the reasons for off-label prescribing, but a historical perspective of sedative and hypnotic prescribing trends shows a move from barbiturates in the 1920s to the 1950s 15 and then to benzodiazepines from the 1960s, 16 mainly because of safety concerns. More recently there have been increasing concerns about the harms of benzodiazepines, in particular alprazolam 17 which was rescheduled from Schedule 4 to 8 in 2014.…”

Section: Limited-evidence Prescribing Practicesmentioning

confidence: 99%

Concerns about quetiapine

Brett¹

2015

Aust Prescr

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“…[10] A substance derived from mephenesin, meprobamate(Equanil r ) was the first tranquillizer marketed in 1955, but it was rapidly rivalled by the benzodiazepines, the first of which, chlordiazepoxide (Librium r ) was developed in 1958 by Leo Sternbach. [11] It was from the structure of a phenothiazine, which produced chlorpromazine, the first antipsychotic, and imipramine, the first antidepressant, that chlordiazepoxide was developed. Its metabolite, diazepam (Valium r ) was for some years the world leader in tranquillizers following its marketing in 1963.…”

Section: Addiction: From Natural Substances To Synthetic Psychotropicsmentioning

confidence: 99%

Addiction, Experimental Models and Neurobiological Mechanisms

Bordet¹

2015

Therapies

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-Humans have constantly sought to alleviate their existential anxieties, first resorting to substances found in their natural environment, and more recently, with the arrival of modern chemistry, using synthetic substances or medications. The substances used in this way are constantly renewing, warranting health surveillance and particular vigilance towards the addictive risk, given its major medical and social impact. This surveillance and vigilance requires detailed, accurate knowledge of the pharmacological and physio-pathological models involved in the emergence of the process of addiction, in particular disturbances of the systems regulating dopaminergic transfer; it also requires knowledge of the means to identify individual risk factors linked to genetic or psycho-behavioural susceptibilities.

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The discovery of chlordiazepoxide and the clinical introduction of benzodiazepines: Half a century of anxiolytic drugs

Cited by 99 publications

References 51 publications

Serotonin, but not dopamine, controls stress response and anxiety-like behavior in crayfish, Procambarus clarkii.

Serotonin, but not dopamine, controls stress response and anxiety-like behavior in crayfish, Procambarus clarkii.

Concerns about quetiapine

Addiction, Experimental Models and Neurobiological Mechanisms

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