Effects of N-methylnaloxone and N-methylanaltrexone on nociception and precipitated abstinence in mice

Antagonism of peripheral opioid receptors by methylnaltrexone does not prevent morphine tolerance in rats

“…These results suggest that peripheral opioid receptors do not contribute to the antinociceptive effect of morphine in these acute pain models in the rat. These results are in line with the earlier studies where small and moderate doses (below 10 mg/kg) of MNTX had no effect on antinociception (Bianchi, Fiocchi, Tavani, & Manara, 1982;Brown, Robertson, & Goldberg, 1983;Brown & Goldberg, 1985;Corder et al, 2017;Ramabadran, 1982;Russell, Bass, Goldberg, Schuster, & Merz, 1982).…”

Acute opioid dependence: characterizing the early adaptations underlying drug withdrawal

“…rather than systemic route (Adams and Holtzman 1991), implicating central rather than peripheral opioid receptor involvement. Central mediation of acute dependence is also suggested by the findings that quaternary derivatives of opioid antagonists, which have poor penetration of the blood-brain barrier (Tavani et al 1979), are relatively ineffective in precipitating jumping and somatic signs in morphine-pretreated rodents (Ramabadran 1982). In addition to these general similarities in receptor mediation, both acute and chronic dependence also appear to be regulated by similar opioid receptor subtypes.…”

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

“…In mouse models without inflammation, increased hot plate latencies after systemic morphine application were inhibited by 50% after naloxone methiodide treatment (Lewanowitsch and Irvine, 2002). Others reported that naloxone methiodide had no effect on opioid analgesia (Ramabadran, 1982;Ramabadran et al, 1982), but at much lower doses than those examined in the study by Lewanowitsch and Irvine (2002). Human studies indicate that opioid agonists that do not readily cross the blood-brain barrier (e.g., morphine-6-glucuronide) are beneficial in patients with visceral and neuropathic pain (Eisenach et al, 2003;Wallace et al, 2006;Mangel et al, 2008) and can have the same analgesic efficacy as conventional opioids, with significantly fewer central nervous system side effects (Tegeder et al, 2003;Hanna et al, 2005;van Dorp et al, 2008).…”