Selective kappa opioid antagonists for treatment of addiction, are we there yet?

Helal, Mohamed A.; Habib, Eman S.; Chittiboyina, Amar G.

doi:10.1016/j.ejmech.2017.10.012

Cited by 32 publications

(20 citation statements)

References 82 publications

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“…On the other hand, antagonists of -ORs were found to block depression, anxiety, and drug-seeking behaviors in animal models. Recently, selective -OR antagonists have been developed as an addiction treatment that does not cause dependence (38). One novel approach in experimental therapeutics for visceral pain combines analgesia from -OR agonism and the antiaddictive effects of a -OR antagonist.…”

Section: Buprenorphine Analogsmentioning

confidence: 99%

Toward an effective peripheral visceral analgesic: responding to the national opioid crisis

Camilleri

2018

American Journal of Physiology-Gastrointestinal and Liver Physi

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This minireiew summarizes recent new developments in visceral analgesics. This promising field is important, as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors via biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor, or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs. Other compounds target nonopioid mechanisms, including cannabinoid (CB2), N-methyl-d-aspartate, calcitonin gene-related peptide, estrogen, and adenosine A receptors and transient receptor potential (TRP) channels (TRPV1, TRPV4, and TRPM8). Although current evidence is based predominantly on animal models of visceral pain, early human studies also support the evidence from the basic and animal research. This augurs well for the development of nonaddictive, visceral analgesics for treatment of chronic abdominal pain, an unmet clinical need.

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Section: Buprenorphine Analogsmentioning

confidence: 99%

Toward an effective peripheral visceral analgesic: responding to the national opioid crisis

Camilleri

2018

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…It can be metabolized into morphine-6-glucuronide (M6G) which accounts for its analgesic effect, and morphine-3-glucuronide (M3G) which accounts for its neuroexcitatory effects 45,46 . There are three types of opioid receptors: mu, delta, kappa 38 . Opioid molecules bind mu opioid receptors (MOR) in the brain to produce both analgesia and euphoria 45,47 .…”

Section: Narcotics and Addictionmentioning

confidence: 99%

“…MOR agonist use, also for treating opioid addiction such as methadone 56 , often leads to frequent relapse. Buprenorphine, a kappa antagonist and partial MOR agonist, has also been used for addiction treatment 38,56 . Several studies were devoted to finding elective kappa opioid antagonists as effective drugs for treatment of addiction 38 .…”

Section: Narcotics and Addictionmentioning

confidence: 99%

Narcotic Addiction in Failed Back Surgery Syndrome

2018

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Back pain is a common health problem that reduces the quality of life for human beings worldwide. Several treatment modalities have been reported as effective for pain relief. Generally, patients often undergo surgical interventions as pain becomes intractable, after conservative treatment. With advances in surgical techniques, those choosing spinal surgery as an option have increased over time, and instrumentation is more popular than it was years ago. However, some patients still have back pain after spinal operations. The number of patients classified as having failed back surgery syndrome (FBSS) has increased over time as has the requirement for patients receiving long-term analgesics. Because pain relief is regarded as a human right, narcotics were prescribed more frequently than before. Narcotic addiction in patients with FBSS has become an important issue. Here, we review the prevalence of FBSS, the mechanism of narcotic addiction, and their correlations. Additionally, several potentially effective strategies for the prevention and treatment of narcotic addiction in FBSS patients are evaluated and discussed.

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“…Kappa opioid receptors (KORs) are the most abundant opioid receptors in the brain [1] with widespread distribution in areas highly linked to stress and reward [2][3][4]. Unlike the reinforcing mu (MOR) and delta (DOR) opioid receptors [1], KOR has high selectivity for endogenous dynorphins (as opposed to enkephalins) [5] and stimulation of KORs are aversive, sometimes referred as an "anti-reward" or stress system [6,7].…”

Section: Introductionmentioning

confidence: 99%

Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers

Matuskey

Dias

Naganawa

et al. 2019

Neuropsychopharmacol.

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Kappa opioid receptors (KORs) have been characterized as an aversive system in the brain and implicated in social behavior in preclinical models. This work investigated the effect of social status on the KOR system in humans using positron emission tomography (PET) imaging with the novel KOR agonist radiotracer [ 11 C]EKAP. Eighteen healthy participants (mean age 41.2 ± 9.3) completed the Barratt Simplified Measure of Social Status (BSMSS), an MRI and an [ 11 C]EKAP PET scan on the High Resolution Research Tomograph. Arterial blood sampling and metabolite analysis were conducted to obtain the input function. Regions of interest were based upon an MR template and included the reward/aversion areas of the brain. The multilinear analysis-1 (MA1) method was applied to the regional time-activity curves (TACs) to calculate [ 11 C]EKAP regional volume of distribution (V T). Mixed models and Pearson correlation coefficients were used for body mass index (BMI), gender and age, with age being dropped in subsequent analyses because of nonsignificance. An overall effect of primary ROIs (F 7, 112 7.43, p < 0.0001), BSMSS score (F 1, 13 7.45, p = 0.02), BMI (F 1, 13 23.5, p < 0.001), and gender (F 1, 13 23.75, p < 0.001), but not age (F 1, 13 1.12, p = 0.35) was observed. Regional [ 11 C]EKAP V T and BSMSS were found to be negatively correlated in the amygdala (r = −0.69, p < 0.01), anterior cingulate cortex (r = −0.56, p = 0.02), caudate (r = −0.66, p < 0.01), frontal cortex (r = −0.52, p = 0.04), hippocampus (r = −0.60, p = 0.01), pallidum (r = −0.59, p = 0.02), putamen (r = −0.62, p = 0.01), and ventral striatum (r = −0.66, p < 0.01). In secondary (non-reward) regions, correlations of [ 11 C]EKAP V T and BSMSS were nonsignificant with the exception of the insula. There was an inverse correlation between social status and KOR levels that was largely specific to the reward/aversion (e.g., saliency) areas of the brain. This finding suggests the KOR system may act as a mediator for the negative effects of social behaviors in humans.

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Selective kappa opioid antagonists for treatment of addiction, are we there yet?

Cited by 32 publications

References 82 publications

Toward an effective peripheral visceral analgesic: responding to the national opioid crisis

Toward an effective peripheral visceral analgesic: responding to the national opioid crisis

Narcotic Addiction in Failed Back Surgery Syndrome

Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers

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