Screening of codeine, dextromethorphan & dextropropoxyphene for their genotoxicity in Swiss albino mice.
OBJECTIVE
It is mandatory for all new drugs to be tested for their potential genotoxicity in addition to general toxicity testing. Some old drugs have not been tested adequately for their genotoxic effects as these were in use before the regulations were enforced. The present study therefore aims to explore the genotoxic potential of some commonly used opioids like codeine, dextromethorphan and dextropropoxyphene in swiss albino mice.


METHODS
Therapeutic equivalent doses of codeine, dextromethorphan and dextropropoxyphene were given orally. Single dose for acute study and multiple doses (repeated every 24 h for 7 times) in additional groups of mice (n=5 in each) for subacute study. Cyclophosphamide served as positive control while normal saline as negative control. About 0.5 ml of blood was collected by retroorbital sinus for comet assay and later the mice were sacrificed to aspirate the femoral bone marrow for micronucleus test. Percentage of micronucleated polychromatic erythrocytes (MnPCE) and comet tail length were calculated in micronucleus assay and comet assay respectively, which served as markers of genotoxicity.


RESULTS
Significant (P<0.001) increase in comet tail length and % MnPCE was observed in both acute and subacute studies of cyclophosphamide group, whereas codeine, dextromethorphan and dextropropoxyphene treated groups did not show any significant changes.


CONCLUSIONS
The results indicated that codeine, dextromethorphan and dextropropoxyphene were devoid of genotoxicity in mice.
Mittal
R
R
Department of Pharmacology & Pharmacotherapeutics, J.N. Medical College, Belgaum, India.
Patil
P A
PA
Torgal
S S
SS
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology; D003061:Codeine / Q000494:pharmacology*; D020552:Comet Assay; D003520:Cyclophosphamide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D003915:Dextromethorphan / Q000494:pharmacology*; D011431:Dextropropoxyphene / Q000494:pharmacology*; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000494:pharmacology*; D011247:Pregnancy
D000701:Analgesics, Opioid; D000996:Antitussive Agents; D009153:Mutagens; D003915:Dextromethorphan; D003520:Cyclophosphamide; D004247:DNA; D011431:Dextropropoxyphene; D003061:Codeine