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New morpholine analogues of phencyclidine: chemical synthesis and pain perception in rats.

Abstract
Phencyclidine (PCP, I) and most its derivatives have demonstrated some pharmacological effects. Accordingly, in this study, the new methoxy (III) and hydroxy-methyl (IV) morpholine PCP derivatives were synthesized. The acute and chronic pain activities of these drugs (III, IV) were investigated by tail immersion and formalin tests on rats and the results were compared with those in PCP, PCM (PCP-morpholine, II), and methyl-PCM (V). Findings indicated that III (6 mg/kg, i.p.) generates more analgesic effects in tail immersion test in comparison with I and II in 20, 40, 45 and 55 min post-injection. These effects were observed in 10, 20, 40, 45 and 50 min after the application of IV (at the same dosage). This analgesic effect was markedly seen in 20, 40, 45 and 50 min after compound IV's application in comparison with the drugs (I-V). In formalin test analysis, the acute chemical pain (Phase I) could not be affected by any drugs (I-V) while chronic formalin pain would be diminished by these new synthesized drugs (III and IV), especially in late Phase II, compared to I and II at the dosage of 6 mg/kg. It is, therefore, concluded that these new synthesized PCP derivates including methoxy-PCM (III) and hydroxy-methyl-PCM (IV) could substantially and respectively diminish acute thermal and chronic chemical pains.
AuthorsAbbas Ahmadi, Mohsen Khalili, Ramin Hajikhani, Moslem Naserbakht
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 98 Issue 2 Pg. 227-33 (Apr 2011) ISSN: 1873-5177 [Electronic] United States
PMID21215770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Inc. All rights reserved.
Chemical References
  • Analgesics
  • Phencyclidine
Topics
  • Analgesics (chemical synthesis, chemistry, pharmacology)
  • Animals
  • Female
  • Models, Animal
  • Pain Measurement
  • Pain Perception (drug effects)
  • Phencyclidine (analogs & derivatives, chemical synthesis, pharmacology)
  • Rats
  • Structure-Activity Relationship

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