TY - JOUR
T1 - Neurotoxicity of dextrorphan
AU - Ortiz, Genaro G.
AU - Guerrero, Juan M.
AU - Reiter, Russel J.
AU - Poeggeler, Burkhard H.
AU - Bitzer-Quintero, Oscar K.
AU - Feria-Velasco, Alfredo
PY - 1999/3
Y1 - 1999/3
N2 - 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.
AB - 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.
KW - Dextrorphan
KW - NMDA antagonists
KW - Neurotoxicity
KW - Posterior cingulate cortex
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U2 - 10.1016/S0188-0128(98)00020-7
DO - 10.1016/S0188-0128(98)00020-7
M3 - Article
C2 - 10372446
AN - SCOPUS:0032985120
VL - 30
SP - 125
EP - 127
JO - Archives of Medical Research
JF - Archives of Medical Research
SN - 0188-4409
IS - 2
ER -