Antinociceptive effects and toxicity of morphine-6-O-sulfate sodium salt in rat models of pain.

Mu-opioids (i.e. morphine, oxycodone, hydrocodone) are considered to be the primary drugs for treatment of moderate to severe acute, chronic and cancer pain.

The analgesic and toxic effects of nornicotine enantiomers alone and in interaction with morphine in rodent models of acute and persistent pain.

Neuronal nicotinic acetylcholinic receptors (nAChR) are promising targets for the development of novel analgesics. Nicotine and other nAChR-agonists produce profound analgesia in rodent models of acute and persistent pain. However, significant side-effects are of concern.

Effects of norketamine enantiomers in rodent models of persistent pain.

NMDA-receptor antagonists are potential drugs for chronic pain treatment, in particular for neuropathic pain involving central sensitization processes. Clinical use of available NMDA antagonists, such as ketamine, is limited for this indication due to its side effects (psychotomimetic, sedative, motor). There is a need for novel NMDA-receptor antagonist(s) with better analgesia/toxicity profile(s).

Interaction between morphine and norketamine enantiomers in rodent models of nociception.

Ketamine, one of a few clinically-available N-Methyl-D-aspartate (NMDA)-receptor antagonists, is known to improve the analgesic efficacy of opioids in humans and rodents. However, the use of ketamine in combination with opioids is mainly restricted to the perioperative setting, due to severe psychotomimetic, sedative and motor side effects. Recent data from our laboratory demonstrated that a major metabolite of ketamine, norketamine, in particular the S(+) enantiomer, had a better antinociception/side effects profile than ketamine in rats.