Exogenous gaseous superoxide potentiates the antinociceptive effect of opioid analgesic agents

1996 ◽  
Vol 45 (9) ◽  
pp. 473-478 ◽  
Author(s):  
N. Goldstein ◽  
T. Lewin ◽  
A. Kamensky ◽  
V. Dubinin ◽  
S. Baumann ◽  
...  
Keyword(s):  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Analgesic Agents

Transmodulation of Dopaminergic Signaling to Mitigate Hypodopminergia and Pharmaceutical Opioid-induced Hyperalgesia

2020 ◽  
Vol 9 (3) ◽  
pp. 164-184
Author(s):  
Raymond Brewer ◽  
Kenneth Blum ◽  
Abdalla Bowirrat ◽  
Edward J. Modestino ◽  
David Baron ◽  
...  
Keyword(s):  
Opioid Analgesic ◽  
Opioid Analgesics ◽  
Well Being ◽  
Deficiency Syndrome ◽  
Pain Tolerance ◽  
Opioid Agonist ◽  
Opioid Agonist Therapy ◽  
Analgesic Agents ◽  
Opioid Induced Hyperalgesia ◽  
Intensive Investigation

Neuroscientists and psychiatrists working in the areas of “pain and addiction” are asked in this perspective article to reconsider the current use of dopaminergic blockade (like chronic opioid agonist therapy), and instead to consider induction of dopamine homeostasis by putative pro-dopamine regulation. Pro-dopamine regulation could help pharmaceutical opioid analgesic agents to mitigate hypodopaminergia-induced hyperalgesia by inducing transmodulation of dopaminergic signaling. An optimistic view is that early predisposition to diagnosis based on genetic testing, (pharmacogenetic/pharmacogenomic monitoring), combined with appropriate urine drug screening, and treatment with pro-dopamine regulators, could conceivably reduce stress, craving, relapse, enhance well-being and attenuate unwanted hyperalgesia. These concepts require intensive investigation. However, based on the rationale provided herein, there is a good chance that combining opioid analgesics with genetically directed pro-dopamine-regulation using KB220 (supported by 43 clinical studies). This prodopamine regulator may become a front-line technology with the potential to overcome, in part, the current heightened rates of chronic opioid-induced hyperalgesia and concomitant Reward Deficiency Syndrome (RDS) behaviors. Current research does support the hypothesis that low or hypodopaminergic function in the brain may predispose individuals to low pain tolerance or hyperalgesia.

Meptazinol Overdose Producing Near Fatal Respiratory Depression

1987 ◽  
Vol 6 (4) ◽  
pp. 331-331 ◽  
Author(s):  
A.G. Davison ◽  
P.O. Collinson ◽  
A.R. Assefi ◽  
S.W. Clarke
Keyword(s):  
Respiratory Depression ◽  
Opioid Analgesic ◽  
Oral Formulation ◽  
Respiratory Arrest ◽  
Analgesic Agents ◽  
Clinically Significant

Meptazinol is one of the new powerful opioid analgesic agents, and an oral formulation has recently been marketed. Clinically significant respiratory depression is said to be absent1 and no overdoses from meptazinol have been reported in the literature. We report a patient who had a respiratory arrest following an overdose of meptazinol.

scholarly journals Designing Opioids That Deter Abuse

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Robert B. Raffa ◽  
Joseph V. Pergolizzi ◽  
Edmundo Muñiz ◽  
Robert Taylor ◽  
Jason Pergolizzi
Keyword(s):  
Current Knowledge ◽  
Opioid Analgesic ◽  
Opioid Abuse ◽  
Prescription Opioid ◽  
Opioid Agonist ◽  
Biological Targets ◽  
Actual Use ◽  
Analgesic Agents ◽  
Physical Barriers ◽  
Public Health Challenge

Prescription opioid formulations designed to resist or deter abuse are an important step in reducing opioid abuse. In creating these new formulations, the paradigm of drug development target should be introduced. Biological targets relating to the nature of addiction may pose insurmountable hurdles based on our current knowledge and technology, but products that use behavioral targets seem logical and feasible. The population of opioid abusers is large and diverse so behavioral targets are more challenging than they appear at first glance. Furthermore, we need to find ways to correlate behavioral observations of drug liking to actual use and abuse patterns. This may involve revisiting some pharmacodynamic concepts in light of drug effect rather than peak concentration. In this paper we present several new opioid analgesic agents designed to resist or deter abuse using physical barriers, the inclusion of an opioid agonist or antagonist, an aversive agent, and a prodrug formulation. Further, this paper also provides insight into the challenges facing drug discovery in this field. Designing and screening for opioids intended to resist or deter abuse is an important step to meet the public health challenge of burgeoning prescription opioid abuse.

Opioid Analgesic Agents and Cancer Cell Biology

2015 ◽  
Vol 5 (3) ◽  
pp. 278-284 ◽  
Author(s):  
Nan Xie ◽  
Marie-Odile Parat
Keyword(s):  
Cancer Cell ◽  
Cell Biology ◽  
Opioid Analgesic ◽  
Analgesic Agents

Synergistic Antinociceptive Effect of Amitriptyline and Morphine in the Rat Orofacial Formalin Test

2004 ◽  
Vol 100 (3) ◽  
pp. 690-696 ◽  
Author(s):  
Philippe Luccarini ◽  
Laurent Perrier ◽  
Céline Dégoulange ◽  
Anne-Marie Gaydier ◽  
Radhouane Dallel
Keyword(s):  
Confidence Interval ◽  
Inflammatory Pain ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Second Phase ◽  
Isobolographic Analysis ◽  
Antinociceptive Effects ◽  
Analgesic Agents ◽  
Rubbing Behavior ◽  
Orofacial Formalin Test

Background Combination therapy is often used to increase the clinical utility of analgesic agents. The coadministration of two compounds may achieve analgesia at doses lower than those required for either compound alone, leading to enhanced pain relief and reduction of adverse effects. Herein, the authors describe the effect of coadministration of morphine and amitriptyline on cutaneous orofacial inflammatory pain in rats. Methods Amitriptyline, morphine, or the combination of amitriptyline and morphine was administered systemically to rats, and antinociceptive effects were determined by means of the rat orofacial formalin test. Isobolographic analysis was used to define the nature of the interactions between morphine and amitriptyline. Results Amitriptyline as well as morphine produced a dose-related inhibition in the first phase and the second phase of rubbing activity. ED50 values against rubbing behavior were 14.6 mg/kg (95% confidence interval, 10.2-33.5 mg/kg) and 1.3 mg/kg (95% confidence interval, 1.0-1.7 mg/kg) for amitriptyline and morphine, respectively. Combinations of increasing fractional increments of amitriptyline and morphine ED50 doses produced a synergistic effect against rubbing behavior, as revealed by isobolographic analysis. Conclusions The current study suggests that systemic amitriptyline and morphine synergistically inhibit cutaneous orofacial inflammatory pain in rats.

Centrally-acting non-opioid analgesic agents

Pain ◽  
1987 ◽  
Vol 30 ◽  
pp. S219
Author(s):  
Ilmar Jurna
Keyword(s):  
Opioid Analgesic ◽  
Analgesic Agents

Recovery after a lumbar disc herniation is dependent on a gender and OPRM1 Asn40Asp genotype interaction

2012 ◽  
Vol 3 (3) ◽  
pp. 182
Author(s):  
M.B. Olsen ◽  
L.M. Jacobsen ◽  
E.I. Schistad ◽  
L.M. Pedersen ◽  
L.J. Rygh ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Lumbar Disc Herniation ◽  
Disc Herniation ◽  
Lumbar Disc ◽  
Opioid Analgesic ◽  
University Hospital ◽  
Endogenous Opioid ◽  
Discogenic Low Back Pain ◽  
Analgesic Agents ◽  
Exon 1

AbstractBackground/aimsThe μ-opioid receptor (OPRM1) is the major target of endogenous opioid peptides and opioid analgesic agents. An important single nucleotide polymorphism (SNP) in this gene is the functional SNP, rs1799971, leading to a substitution of asparagine (Asn) to aspartic acid (Asp) at codon 40 in exon 1. Previous studies have suggested that this SNP may give different phenotypes in males and females. In the present study we therefore investigated whether the OPRM1 Asn40Asp SNP, grouped by gender, could predict clinical outcome regarding progression of pain intensity and disability in patients with discogenic low back pain and sciatica.MethodsPatients (n = 252) with lumbar disc herniation and sciatic pain, all European-caucasian, were recruited from Oslo University Hospital Ullevål and Haukeland University Hospital. Blood samples were drawn, genomic DNA isolated and the OPRM1 Asn40Asp SNP was detected by TaqMan methodology. Pain intensity and functional consequences were rated on a visual analogue scale (VAS), by McGill Sensory and by Oswestry Disability Index (ODI) over a 12 months period (inclusion, 6 weeks, 6 months and 12 months).ResultsThe genotype */Asp was associated with more pain in women, but seemed to protect the men from pain after lumbar disc herniation. Wildtype Asn/Asn women and men reported similar pain ratings. Analysis of the recovery for the four groups; women Asn/Asn, women */Asp, men Asn/Asn and men */Asp, showed that the */Asp women had a significantly slower recovery, i.e., pain intensity over time than the */Asp men (VAS activity score p = 0.002, McGill sense score p = 0.021, ODI p = 0.205, rmANOVA including covariates smoke, treatment and age with p ≤ 0.1).ConclusionThe present data suggest that the OPRM1 Asp variant increases the pain intensity in women, but have the opposite effect on men the first year after a disc herniation.

Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa

Life Sciences ◽  
2004 ◽  
Vol 74 (17) ◽  
pp. 2143-2155 ◽  
Author(s):  
Kenjiro Matsumoto ◽  
Syunji Horie ◽  
Hayato Ishikawa ◽  
Hiromitsu Takayama ◽  
Norio Aimi ◽  
...  
Keyword(s):  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Medicinal Herb ◽  
Mitragyna Speciosa ◽  
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