Neurotoxicity of dextrorphan.
BACKGROUND
The noncompetitive NMDA antagonists phencyclidine (PCP) and dizocilpine (MK-801) have been considered for use as neuroprotective therapeutic agents, although both produce injury in neurons of cingulate and retrosplenial cortices in rodents. The low-affinity, noncompetitive NMDA antagonist dextrorphan has been considered for use as a neuroprotective therapeutic drug. The aim of the present work was to evaluate the neurotoxicity of dextrorphan.


METHODS
Sprague-Dawley male rats were used and injected with either saline or dextrorphan (30 mg/kg i.p.). The animals were sacrificed 30 min later, and the brain was examined for histopathological changes.


RESULTS
After systemic administration of the drug, hyperchromatic and shrunken nuclei with chromatin condensation and disruption were observed. Also, granular and vacuolated cytoplasm was apparent in pyramidal neurons in the retrosplenial (posterior cingulate) cortex. Status spongiosus (spongy degeneration) of the neuropil was also detected.


CONCLUSIONS
Morphological changes are similar to those described previously, which are induced by high-affinity, noncompetitive NMDA antagonists, such as MK-801.
Ortiz
G G
GG
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, USA. orve@foreigner.class.udg.mx
Guerrero
J M
JM
Reiter
R J
RJ
Poeggeler
B H
BH
Bitzer-Quintero
O K
OK
Feria-Velasco
A
A
D000818:Animals; D001921:Brain / Q000187:drug effects; D003917:Dextrorphan / Q000009:adverse effects*; D008297:Male; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D003917:Dextrorphan