Understanding the pharmacokinetics of anxiolytic drugs

Altamura, Alfredo Carlo; Moliterno, D.; Paletta, Silvia; Maffini, M.; Mauri, Massimo C.; Bareggi, Silvio R.

doi:10.1517/17425255.2013.759209

Cited by 78 publications

(65 citation statements)

References 118 publications

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“…Diazepam is a classic anxiolytic, which has been demonstrated in numerous clinical studies [42] and various animal models with pain [40,43]. The present study also observed anxiolytic effect of diazepam in the acid-induced CWP model.…”

Section: Research Fu-zen Shawsupporting

confidence: 80%

Pregabalin, Duloxetine, and Diazepam Selectively Modulate Acid-Induced Hyperalgesia and Anxio-Depressive Comorbidity in Rats

Liu¹,

Chen²,

Chuang³

et al. 2017

Neuropsychiatry

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Objective:Patients with chronic widespread pain (CWP) syndrome often have comorbid with depression/ anxiety symptoms and unsatisfied. Effects of pregabalin, duloxetine and diazepam in the well-established acid-induced CWP model remain unclear. This study aimed to assess these medicines on mechanical hyperalgesia and psychiatric comorbidity in this CWP model. Methods:The CWP model was elicited by repeated injections of acidic solution into unilateral gastrocnemius muscle of a rat. Each medicine was administered orally via gavage twice per day for >2 weeks. Paw withdrawal threshold (PWT) was evaluated by von Frey filaments. Anxiety-like behavior was assessed by an elevated plus maze. Despair mood and anhedonia of depression-like behavior were evaluated using the forced swimming and sucrose preference tests, respectively. Results:Rats receiving acid injections displayed bilateral hyperalgesia and anxio-depressive comorbidity. Pregabalin significantly increased PWTs and ameliorated anxiety-like and anhedonic behaviours. Duloxetine significantly increased PWTs and ameliorated depressionlike but not anxiety-like behaviour. Diazepam did not alter PWTs but remedied anxiety-like and anhedonic behaviours. Pregabalin, duloxetine, and diazepam revealed different effects on hyperalgesia and anxio-depressive comorbidity in the acid-induced CWP model. Conclusion:Our results strengthen the acid-induced pain model as humans with CWP on additional evidences of face and predictive validities. This study provides information of these medicines on selective treatment of pain and psychiatric comorbidity. Keywords:Muscle pain, Fibromyalgia, Pregabalin, Duloxetine, Diazepam, Anxiety, Depression Neuropsychiatry (London) (2017) 7(6) 850Research Fu-Zen Shaw via gavage. We hypothesized that these drugs would selectively modulate hyperalgesia and comorbidity of anxiety-and depression-like behaviors in the acid-induced CWP animal model. The results of this study provided predictive validity between acid-induced muscle pain in CWP animal model and patients with CWP syndromes and also extended our understanding of these medicines on CWP syndromes and psychiatric comorbidity. MethodsMale Sprague-Dawley rats (8-9 weeks old) were kept in a sound-attenuated room under a 12/12-h light/dark cycle (lights on at 06:00-18:00) with food and water provided ad libitum. The rats were randomly assigned into a group receiving the vehicle (pH 7.2) or acidic saline (pH 4.0) at a ratio of 1:1

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Section: Research Fu-zen Shawsupporting

confidence: 80%

Pregabalin, Duloxetine, and Diazepam Selectively Modulate Acid-Induced Hyperalgesia and Anxio-Depressive Comorbidity in Rats

Liu¹,

Chen²,

Chuang³

et al. 2017

Neuropsychiatry

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“…To determine whether these anxiety-related behaviors observed in CD157 −/− mice can be rescued through pharmacological treatment, we examined diazepam (Altamura et al, 2013), an anti-anxiety drug that activates GABA A receptors and mirtazapine (Watanabe et al, 2011), a second-generation anti-depressant with a combined serotonergic and noradrenergic mechanism. Based upon preparatory experiments for determining drug doses, we used diazepam with a concentration of 1 mg/kg in a single i.p.…”

Section: Resultsmentioning

confidence: 99%

Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson's disease

Lopatina

Yoshihara

Nishimura

et al. 2014

Front. Behav. Neurosci.

127

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CD157, known as bone marrow stromal cell antigen-1, is a glycosylphosphatidylinositol-anchored ADP-ribosyl cyclase that supports the survival and function of B-lymphocytes and hematopoietic or intestinal stem cells. Although CD157/Bst1 is a risk locus in Parkinson's disease (PD), little is known about the function of CD157 in the nervous system and contribution to PD progression. Here, we show that no apparent motor dysfunction was observed in young knockout (CD157−/−) male mice under less aging-related effects on behaviors. CD157−/− mice exhibited anxiety-related and depression-like behaviors compared with wild-type mice. These behaviors were rescued through treatment with anti-psychiatric drugs and oxytocin. CD157 was weakly expressed in the amygdala and c-Fos immunoreactivity in the amygdala was less evident in CD157−/− mice than in wild-type mice. These results demonstrate for the first time that CD157 plays a role as a neuro-regulator and suggest a potential role in pre-motor symptoms in PD.

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“…35–37 Although some BZDs, such as oxazepam, lorazepam, and temazepam, are directly conjugated via glucuronyl transferase, others, such as alprazolam and diazepam, are first metabolized by the CYP isozyme 3A4 and/or 3A5. 36 Thus, when certain BZDs are coadministered with inhibitors of the CYP system, one would expect a decrease in BZD clearance associated with potentially increased somnolence and respiratory depression, especially when combined with opioids. 35,36 …”

Section: Prevalence and Risk Factorsmentioning

confidence: 99%

“…36 Thus, when certain BZDs are coadministered with inhibitors of the CYP system, one would expect a decrease in BZD clearance associated with potentially increased somnolence and respiratory depression, especially when combined with opioids. 35,36 …”

Section: Prevalence and Risk Factorsmentioning

confidence: 99%

Risks, Management, and Monitoring of Combination Opioid, Benzodiazepines, and/or Alcohol Use

Gudin

Mogali

Jones

et al. 2013

Postgraduate Medicine

195

122

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The concurrent use of opioids, benzodiazepines (BZDs), and/or alcohol poses a formidable challenge for clinicians who manage chronic pain. While the escalating use of opioid analgesics for the treatment of chronic pain and the concomitant rise in opioid-related abuse and misuse are widely recognized trends, the contribution of combination use of BZDs, alcohol, and/or other sedative agents to opioid-related morbidity and mortality is underappreciated, even when these agents are used appropriately. Patients with chronic pain who use opioid analgesics along with BZDs and/or alcohol are at higher risk for fatal/nonfatal overdose and have more aberrant behaviors. Few practice guidelines for BZD treatment are readily available, especially when they are combined clinically with opioid analgesics and other central nervous system–depressant agents. However, coadministration of these agents produces a defined increase in rates of adverse events, overdose, and death, warranting close monitoring and consideration when treating patients with pain. To improve patient outcomes, ongoing screening for aberrant behavior, monitoring of treatment compliance, documentation of medical necessity, and the adjustment of treatment to clinical changes are essential. In this article, we review the prevalence and pharmacologic consequences of BZDs and/or alcohol use among patients with pain on chronic opioid therapy, as well as the importance of urine drug testing, an indispensable tool for therapeutic drug monitoring, which helps to ensure the continued safety of patients. Regardless of risk or known aberrant drug-related behaviors, patients on chronic opioid therapy should periodically undergo urine drug testing to confirm adherence to the treatment plan.

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Understanding the pharmacokinetics of anxiolytic drugs

Cited by 78 publications

References 118 publications

Pregabalin, Duloxetine, and Diazepam Selectively Modulate Acid-Induced Hyperalgesia and Anxio-Depressive Comorbidity in Rats

Pregabalin, Duloxetine, and Diazepam Selectively Modulate Acid-Induced Hyperalgesia and Anxio-Depressive Comorbidity in Rats

Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson's disease

Risks, Management, and Monitoring of Combination Opioid, Benzodiazepines, and/or Alcohol Use

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