Articles: narcotic-antagonists.
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Ultra-low doses of opioid receptor antagonists inhibit development of chronic spinal morphine tolerance. As this phenomenon mechanistically resembles acute tolerance, the present study examined actions of opioid receptor antagonists on acute spinal morphine tolerance. In adult rats, administration of three intrathecal injections of morphine (15 microg) at 90 min intervals produced a significant decline of the antinociceptive effect and loss of agonist potency in both the tail-flick and paw-pressure tests. ⋯ The results show that ultra-low doses of opioid receptor antagonists block acute tolerance to morphine. This effect may result from blockade of opioid excitatory effects that produce a latent hyperalgesia that then contributes to induction of tolerance. The sustained antinociception produced by combination of morphine with an opioid receptor antagonist shows dependency on the adenosine receptor activity.
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Alcohol. Clin. Exp. Res. · Apr 2007
Randomized Controlled TrialOpioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study.
Pharmacotherapy of alcohol dependence (AD) is at an early stage of development; currently available medications have limited efficacy. It would be clinically valuable to identify, before initiation of a course of treatment, those patients who, based on genetic markers, are most likely to respond to a specific pharmacotherapy. A previous report suggested that a functional variant at the genetic locus encoding the mu opioid receptor (Asn40Asp) is such a marker, in short-term (3-month) treatment with the opioid-blocking drug naltrexone (NTX). ⋯ These results do not support association of the OPRM1 Asn40Asp polymorphism with NTX treatment response for AD.
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Biological psychology · Apr 2007
Randomized Controlled TrialNociceptive flexion reflex and pain rating responses during endogenous opiate blockade with naltrexone in healthy young adults.
The effect of opioid blockade on nociceptive flexion reflex (NFR) activity and subjective pain ratings was examined in 151 healthy young men and women. Using a within-subjects design, NFR threshold was assessed on 2 days after administration of either placebo or a 50mg dose of naltrexone. Electrocutaneous pain threshold and tolerance levels were measured after NFR threshold assessment on each day. ⋯ Specifically, participants exhibited lower levels of NFR activity and reported lower pain ratings for electrocutaneous stimulation delivered at pain threshold and tolerance levels following administration of naltrexone as compared to placebo. These findings indicate that opiate blockade using the current standard dose may elicit hypoalgesia. A potential moderating effect of dose of opiate-blockade medication and level of endogenous opioid activation should be carefully examined in future research.
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Expert Opin Drug Saf · Mar 2007
ReviewNaloxone treatment in opioid addiction: the risks and benefits.
Naloxone is a non-selective, short-acting opioid receptor antagonist that has a long clinical history of successful use and is presently considered a safe drug over a wide dose range (up to 10 mg). In opioid-dependent patients, naloxone is used in the treatment of opioid-overdose-induced respiratory depression, in (ultra)rapid detoxification and in combination with buprenorphine for maintenance therapy (to prevent intravenous abuse). Risks related to naloxone use in opioid-dependent patients are: i) the induction of an acute withdrawal syndrome (the occurrence of vomiting and aspiration is potentially life threatening); ii) the effect of naloxone may wear off prematurely when used for treatment of opioid-induced respiratory depression; and iii) in patients treated for severe pain with an opioid, high-dose naloxone and/or rapidly infused naloxone may cause catecholamine release and consequently pulmonary edema and cardiac arrhythmias. These risks warrant the cautious use of naloxone and adequate monitoring of the cardiorespiratory status of the patient after naloxone administration where indicated.
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From Australian coronial records, we identified five deaths involving implantable naltrexone between 2000 and 2004. One man died from acute narcotism with a naltrexone implant in place and a blood naltrexone level of 0.3 mg/L. A woman died of combined drug effect (including naltrexone) accompanied by severe pain from a naltrexone implant site. These cases indicate that patients can die from opioid overdose with a naltrexone implant and blood naltrexone levels higher than reported blockade levels.