Screening of codeine, dextromethorphan & dextropropoxyphene for their genotoxicity in swiss albino mice.

Background & objectives: 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 sacrifi ced 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: Signifi cant Signififi (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 signifi cant changes. Interpretation & conclusion: The results indicated that codeine, dextromethorphan and dextropropoxyphene were devoid of genotoxicity in mice.

Effects of dextromethorphan on dopamine dependent behaviours in rats.

Dextromethorphan, a noncompetitive blocker of N-methyl-D- aspartate (NMDA) type of glutamate receptor, at 7.5-75 mg/kg, ip did not induce oral stereotypies or catalepsy and did not antagonize apomorphine stereotypy in rats. These results indicate that dextromethorphan at 7.5-75 mg/kg does not stimulate or block postsynaptic striatal D2 and D1 dopamine (DA) receptors. Pretreatment with 15 and 30 mg/kg dextromethorphan potentiated dexamphetamine stereotypy and antagonised haloperidol catalepsy. Pretreatment with 45, 60 and 75 mg/kg dextromethorphan, which release 5-hydroxytryptamine (5-HT), however, antagonised dexamphetamine stereotypy and potentiated haloperidol catalepsy. Apomorphine stereotypy was not potentiated or antagonised by pretreatment with 7.5-75 mg/kg dextromethorphan. This respectively indicates that at 7.5-75 mg/kg dextromethorphan does not exert facilitatory or inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptors. The results are explained on the basis of dextromethorphan (15-75 mg/kg)-induced blockade of NMDA receptors in striatum and substantia nigra pars compacta. Dextromethorphan at 15 and 30 mg/kg, by blocking NMDA receptors, activates nigrostriatal dopaminergic neurons and thereby potentiates dexampetamine stereotypy and antagonizes haloperidol catalepsy. Dextromethorphan at 45, 60 and 75 mg/kg, by blocking NMDA receptors, releases 5-HT and through the released 5-HT exerts an inhibitory influence on the nigrostriatal dopaminergic neurons with resultant antagonism of dexampetamine stereotypy and potentiation of haloperidol catalepsy.

Abuso de ziprepol: un problema emergente / Ziprepol abuse: an emergent problem

El ziprepol es un medicamento antitusígeno, derivado de piperazina, que en dosis elevadas tiene propiedades adictivas y neurotóxicas. En Chile hay un aumento del abuso de este fármaco por parte de jóvenes, con fines alucinógenos, euforizantes y sedantes. Se analizan las propiedades farmacológicas del ziprepol y las características de la adiccón y de la toxicidad por sobredosis