Competitive and non-competitive NMDA antagonists limit dynorphin A-induced rat hindlimb paralysis

Brain Res. 1990 Jan 15;507(1):1-5. doi: 10.1016/0006-8993(90)90512-a.


It has been proposed that the endogenous opioid dynorphin A (Dyn A) contributes to the pathogenesis of posttraumatic spinal cord injury (SCI). Dyn A-related peptides given intrathecally (i.t.) produce hindlimb paralysis. These include Dyn A(1-17), Dyn A(1-13), Dyn A(2-17), and Dyn A(3-13). Because Dyn A(2-17) and Dyn A(3-13) are inactive at opiate receptors, Dyn A-induced paralysis may include a non-opioid component. Recently, it has been reported that competitive N-methyl-D-aspartate (NMDA) antagonists block the loss of tail-flick reflex caused by i.t. administration of Dyn A(1-13). In the present studies we examined whether competitive [(4-[3-phosphonopropyl]-2-piperazine-carboxylic acid (CPP)] or non-competitive (dextrorphan) NMDA antagonists could attenuate paralysis induced by Dyn A(1-17) or Dyn A(2-17). CPP or dextrorphan each significantly attenuated the neurologic dysfunction and mortality associated with Dyn A(1-17) administration. In addition, CPP and dextrorphan significantly reduced the neurologic dysfunction caused by Dyn A(2-17)(all P less than 0.05). From these data we suggest that the non-opioid component of Dyn A-induced paralysis is mediated in part by the NMDA receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Dextrorphan / pharmacology*
  • Dynorphins / pharmacology*
  • Dynorphins / physiology
  • Hindlimb / physiopathology
  • Male
  • Morphinans / pharmacology*
  • Paralysis / chemically induced*
  • Paralysis / metabolism
  • Peptide Fragments / pharmacology
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*


  • Morphinans
  • Peptide Fragments
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Dextrorphan
  • Dynorphins
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid