10 Matching Annotations
  1. Jan 2019
    1. naltrexone in their drinking water (5 mg/L)

      Based on water intake of 10ml per 100g body mass, that should translate to 0.5 mg/kg. This is one of the few studies using LDN as opposed to ULDN.

    1. inverse agonist activity was not required for mu-opioid receptor up-regulation and supersensitivity.

      The question, then, is whether the opioid receptors are involved at all in this upregulation. For example, it could be mediated by TLR4 or filamin A.

    1. Table 1. Analgesic potency of nalorphine compared with morphine for postoperative pain*

      2 mg appears most effective. download PDF here.

    Tags

    Annotators

    1. . Ultra-low doses of opioid antagonists (naloxone and naltrexone), which selectively inhibit the excitatory effects

      I would not expect doses this small to impact the opioid receptors.

    1. Treatment effects were more pronounced at discharge

      Symptoms in the treatment group continually improved, whereas symptoms in the placebo group plateaued. Thus, I'm interested in seeing a longer treatment period. Projecting from symptom scores, elimination of symptoms would occur in about 10 days.

    1. 50 mg naltrexone at bed-time.

      Interesting. Conventional doses of naltrexone appear effective for sleep apnea. I'll be interested in seeing if LDN fairs well.

  2. Nov 2018
    1. The full text describes how ultra-low-dose naloxone and naltrexone enhance opioids at very slim dose margins. A mere two fold difference on naltrexone dose can determine efficacy: 2 micrograms is effective whereas 4 is not. What's more, this optimal dose changes with sex, mouse strain, opioid agonist used, etc.; this making precise dosing challenging. The mechanism suggested is that filamin A has two binding sites, where only 1 has the desired effect.

    1. We measure the binding affinity of NLX or naltrexone to FLNA in cell membranes as 4 picomolar, i.e. approximately 200-fold higher than their binding affinity for MOR

      This sentence appears to indicate equal potency between the two drugs.

    2. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs.

      So, naloxone has a 200 times higher potency at Filamin A compared to opioid receptors, but I need clarification on whether naltrexone achieves similar potency.

  3. Apr 2018
    1. Naloxone alone has a bimodal effect on analgesia: low intravenous doses (1–2 mg) produce analgesia and higher doses (3+ mg) produce hyperalgesia in healthy normal volunteers (Buchsbaum et al. 1977) and in postoperative patients (Levine et al. 1979). Clinical trials showed that intravenous and epidural opioids combined with naloxone could produce greater analgesia than opioids alone (Rawal et al. 1986; Gueneron et al. 1988; Gan et al. 1997); these studies revealed the importance of the ratio of opioid agonist to antagonist in enhancing analgesia, showing ultra-low naloxone doses (ng/kg to pg/kg) are needed for optimal effect.

      Standard LDN is 4.5mg. According to this data, that may be orders of magnitude too high. Nevertheless, LDN has been found effective.