The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Nov 2019
Behavioral Effects of Opioid Full and Partial Agonists During Chronic Buprenorphine Treatment.
Buprenorphine, a partial agonist at the μ-opioid receptor, is commonly prescribed for the management of opioid addiction. Notwithstanding buprenorphine's clinical popularity, the relationship between its effectiveness in attenuating relapse-related behavior and its opioid efficacy is poorly understood. Furthermore, changes in the antinociceptive potency or effectiveness of opioid drugs that might occur during buprenorphine treatment have not been characterized. ⋯ These results suggest that the utility of buprenorphine in the management of opioid addiction, and how it alters the analgesic effects of opioids, can vary depending on the efficacy of the abused or prescribed opioid. SIGNIFICANCE STATEMENT: Our findings indicate that the pharmacological efficacy of abused opioids may predict the ability of buprenorphine to attenuate their relapse-related priming and analgesia-related antinociceptive effects. This information can help inform physicians as to the effectiveness and limitations of buprenorphine as a pharmacotherapy for opioid addiction.
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J. Pharmacol. Exp. Ther. · Nov 2019
Addressing the Opioid Crisis: Medical Student Instruction in Opioid Drug Pharmacology, Pain Management, and Substance Use Disorders.
The marked increase in deaths related to opioid drugs after 1999 was associated with an increase in the number of prescriptions for opioid drugs. This was accompanied by increasing demand for improved management of chronically painful conditions. These factors suggest that improvements are needed in the education of physicians with regard to the management of chronic pain, the optimal therapeutic application of opioid drugs, and the avoidance of substance use disorders. In this article, we address the evidence that physician education can influence prescribing practices and we discuss approaches to enhance the preclinical and clinical education of medical students in pain management and substance use disorders.
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J. Pharmacol. Exp. Ther. · Nov 2019
Pharmacological Assessment of Sepiapterin Reductase Inhibition on Tactile Response in the Rat.
There is an unmet medical need for nonopioid pain therapies in human populations; several pathways are under investigation for possible therapeutic intervention. Tetrahydrobiopterin (BH4) has received attention recently as a mediator of neuropathic pain. Recent reports have implicated sepiapterin reductase (SPR) in this pain pathway as a regulator of BH4 production. ⋯ SPR inhibition and mechanical allodynia were assessed coordinately with pterin biomarkers in plasma and at the site of neuronal injury (i.e., dorsal root ganglion). Upon daily oral administration for 3 consecutive days, unbound plasma concentrations of test article exceeded the unbound in vivo rat SPR IC90 throughout the dose intervals, leading to a 60% reduction in BH4 in the dorsal root ganglion. Despite evidence for pharmacological modulation of the BH4 pathway, there was no significant effect on the tactile paw withdrawal threshold relative to vehicle-treated controls.