Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics
Final rept. 15 Apr 2007-14 Apr 2010
MICHIGAN UNIV ANN ARBOR
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The studies proposed in this project will test the hypotheses that in the non-human primate 1 the functions and behavioral effects of the NOP receptor are independent of classical opioid receptors, 2 activation of the NOP receptor produces strong antinociception without abuse liability, and 3 NOP receptor agonists possess a promising therapeutic profile as analgesics compared to mu opioids following repeated administration in primates. Several key findings have been obtained and some have been published. First, intrathecal administration of NOFQ only produced antinociception in primates. The functional profiles of spinal NOP receptors are different between primates and rodents. Second, intrathecal administration of NOFQ and other NOP receptor agonists produced antinociception without eliciting itchscratching responses, indicating that NOP receptor agonists represent a therapeutic target as spinal analgesics. Third, NOP receptor agonists produced antinociceptive effects comparable to clinically used mu opioids such as morphine and alfentanil in three different primate pain models, indicating that the analgesic effectiveness of NOP receptor agonists may be similar to that of mu opioid analgesics in humans. Finally, unlike mu opioids, NOP receptor agonists did not produce reinforcing effects, respiratory depressant, sedation, or itchpruritic side effects, indicating that NOP receptor agonists may be a new generation of novel analgesics without abuse liability.
- Medicine and Medical Research