Accession Number : ADA525900


Title :   Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics


Descriptive Note : Final rept. 15 Apr 2007-14 Apr 2010


Corporate Author : MICHIGAN UNIV ANN ARBOR


Personal Author(s) : Ko, Mei-Chuan


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a525900.pdf


Report Date : May 2010


Pagination or Media Count : 71


Abstract : 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 N/OFQ only produced antinociception in primates. The functional profiles of spinal NOP receptors are different between primates and rodents. Second, intrathecal administration of N/OFQ and other NOP receptor agonists produced antinociception without eliciting itch/scratching 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 itch/pruritic side effects, indicating that NOP receptor agonists may be a new generation of novel analgesics without abuse liability.


Descriptors :   *PEPTIDES , *ANALGESICS , *PHARMACOLOGY , SEDATION , RECEPTOR SITES(PHYSIOLOGY) , MORPHINE , PAIN , THERAPY , RESPIRATORY SYSTEM , MEDICAL RESEARCH


Subject Categories : Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE