Article
Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile.
Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group), Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Leicester Royal Infirmary, Leicester, UK.
BJA British Journal of Anaesthesia (impact factor:
4.24).
08/2009;
103(1):38-49.
DOI:10.1093/bja/aep129
pp.38-49
Source: PubMed
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Citations (0)
- Cited In (4)
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Article: The combination of long
[show abstract] [hide abstract]
ABSTRACT: acting opioids has not been sufficiently documented in the literature. Patient J.L., aged 67, with disseminated malignant process. Complaints of pelvic and visceral pain. Treatment: sustained release morphine 60 mg/daily. There oc-curred a need to increase the dose of the drug up to 120 mg/daily; the patient was referred to the Pain Management Outpatient Department. Nociceptive pain was diagnosed at the intensity of 7.5 on the VAS scale. Ketoprofen was included in the treatment at a dose of 200 mg/daily. After three days the mor-phine dose was increased to 180 mg/dai-ly. Due to the lack of adequate pain con-trol sustained release oxycodone was started, initially at a dose of 20 mg/ daily, and after three days 40 mg/daily. After two weeks, the dose of morphine was decreased to 140 mg/daily. Ade-quate pain control was obtained. K Ke ey y w wo or rd ds s: : opioid, morphine, oxycodone, opioid combination, pain management. Efficient management of pain in the course of cancer diseases often en-counters serious difficulties [1, 2]. A very frequent problem is, e.g. concomitant occurrence of many types of pain in the same patient. The course of the dis-ease is often complicated by persistent post-surgical pain, pain related to bone metastases, neurogenic pain, or various types of neuropathic pain due to the infiltration of nerves, post-herpetic neuralgia, or chemotherapy-induced peripheral neuropathy. Unfortunately, very frequently there also occurs a lack of effectiveness of opioids, or a rapid increase in tolerance to the therapy applied. The principles of pain management, coded in the form of the WHO analgesic ladder, on assumption, introduce the principle of combining various drugs in or-der to increase their effectiveness, due to the use of combining and synergis-tic mechanisms [3]. Multimodal therapy in the form of opioids, non-steroid anti-inflammatory drugs (NSAIDs) and co-analgesics, in the majority of cases allows efficient analgesia to be achieved, without the necessity for increasing the dosage of drugs, and often allows reduction of the amount of drugs applied. Simultaneous application of NSAIDs, opioids and co-analgesics, therefore, is the rule [4]; however, the administration of several drugs of the opioids group still evokes controversy. To date, few reports are available concerning the im-plementation of such a method of treatment [5]; therefore, it cannot be con-sidered that there is scientific evidence which would justify such models of therapy [6]. At present, one can only rely on the opinion of experts that con-sidering the variation in opioid receptors and varied susceptibility to exoge-nous ligands used, it is permissible to combine opioid drugs [5, 6].Contemporary Oncology / Wspólczesna Onkologia 01/2011; · 0.06 Impact Factor -
Article: Opioid combination. Case report
[show abstract] [hide abstract]
ABSTRACT: The combination of long-acting opioids has not been sufficiently documented in the literature. Patient J.L., aged 67, with disseminated malignant process. Complaints of pelvic and visceral pain. Treatment: sustained release morphine 60 mg/daily. There oc-curred a need to increase the dose of the drug up to 120 mg/daily; the patient was referred to the Pain Management Outpatient Department. Nociceptive pain was diagnosed at the intensity of 7.5 on the VAS scale. Ketoprofen was included in the treatment at a dose of 200 mg/daily. After three days the mor-phine dose was increased to 180 mg/dai-ly. Due to the lack of adequate pain con-trol sustained release oxycodone was started, initially at a dose of 20 mg/ daily, and after three days 40 mg/daily. After two weeks, the dose of morphine was decreased to 140 mg/daily. Ade-quate pain control was obtained. K Ke ey y w wo or rd ds s: : opioid, morphine, oxycodone, opioid combination, pain management. Efficient management of pain in the course of cancer diseases often en-counters serious difficulties [1, 2]. A very frequent problem is, e.g. concomitant occurrence of many types of pain in the same patient. The course of the dis-ease is often complicated by persistent post-surgical pain, pain related to bone metastases, neurogenic pain, or various types of neuropathic pain due to the infiltration of nerves, post-herpetic neuralgia, or chemotherapy-induced peripheral neuropathy. Unfortunately, very frequently there also occurs a lack of effectiveness of opioids, or a rapid increase in tolerance to the therapy applied. The principles of pain management, coded in the form of the WHO analgesic ladder, on assumption, introduce the principle of combining various drugs in or-der to increase their effectiveness, due to the use of combining and synergis-tic mechanisms [3]. Multimodal therapy in the form of opioids, non-steroid anti-inflammatory drugs (NSAIDs) and co-analgesics, in the majority of cases allows efficient analgesia to be achieved, without the necessity for increasing the dosage of drugs, and often allows reduction of the amount of drugs applied. Simultaneous application of NSAIDs, opioids and co-analgesics, therefore, is the rule [4]; however, the administration of several drugs of the opioids group still evokes controversy. To date, few reports are available concerning the im-plementation of such a method of treatment [5]; therefore, it cannot be con-sidered that there is scientific evidence which would justify such models of therapy [6]. At present, one can only rely on the opinion of experts that con-sidering the variation in opioid receptors and varied susceptibility to exoge-nous ligands used, it is permissible to combine opioid drugs [5, 6].Contemporary Oncology / Wspólczesna Onkologia 01/2011; 15:409-411. · 0.06 Impact Factor -
Article: Opioid Peptidomimetics: Leads for the Design of Bioavailable Mixed Efficacy μ Opioid Receptor (MOR) Agonist/δ Opioid Receptor (DOR) Antagonist Ligands.
[show abstract] [hide abstract]
ABSTRACT: We have previously described opioid peptidomimetic, 1, employing a tetrahydroquinoline scaffold and modeled on a series of cyclic tetrapeptide opioid agonists. We have recently described modifications to these peptides that confer a μ opioid receptor (MOR) agonist, δ opioid receptor (DOR) antagonist profile, which has been shown to reduce the development of tolerance to the analgesic actions of MOR agonists. Several such bifunctional ligands have been reported, but none has been demonstrated to cross the blood-brain barrier. Here we describe the transfer of structural features that evoked MOR agonist/DOR antagonist behavior in the cyclic peptides to the tetrahydroquinoline scaffold and show that the resulting peptidomimetics maintain the desired pharmacological profile. Further, the 4R diastereomer of 1 was fully efficacious and approximately equipotent to morphine in the mouse warm water tail withdrawal assay following intraperitoneal administration and thus a promising lead for the development of opioid analgesics with reduced tolerance.Journal of Medicinal Chemistry 02/2013; · 4.80 Impact Factor
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Keywords
activating MOP
active centres
bivalent ligand
bivalent ligands
blocking DOP
current gold standard analgesic
DOP antagonist naltrindole
drug design
interesting examples
MOP
MOP agonist oxymorphone
MOP receptors
MOP/DOP bivalent ligand
nociceptin/orphainin FQ
non-classical opioid receptor
non-selective drug
Opioid receptors
selective morphine-like
single drug
variably troublesome side-effects
