Clomipramine modulates the effects of codeine, dextromethorphan and dextropropoxyphene on neurotransmitters of normal rats

ABSTRACT

The effect of chronic treatment with dextromethorphan [DM], codeine or dextropropoxyphene [DP] individually or in combination with clomipramine [CIM] on brain gamma aminobutyric acid [GABA], serotonin [5-HT] and cyclic adenosine monophosphate [cAMP], serum transaminase [ALT and AST] and serum electrolytes [Na+, K+ and Ca2+] was studied in this work. Treatment with CIM or DP for 30 days induced a significant reduction in the rat brain GABA content. On the other hand, treatment with codeine induced a significant increase in rat brain GABA content. The concurrent administration of CIM with DM or codeine caused a significant increase in rat brain GABA content. The administration of CIM alone or concomitantly with DM, codeine or DP caused a significant increase in brain 5-HT content. On the other hand, treatment with CIM induced a significant increase in brain cAMP content. However, the administration of DM, codeine or DP individually or in combination with CIM induced a significant decrease in brain cAMP content. All drugs used in the present study alone or in combination induced a significant increase in serum transaminase levels [ALT and AST]. The administration of DP or co-administration of CIM with codeine or DP induced a significant increase in serum sodium level. While, co-administration of CIM with DM induced a significant decrease in serum sodium level. The administration of DM or DP individually or co-administration of CIM with DM codeine or DP induced a significant increase in serum potassium level. In addition, serum calcium level was significantly increased as a result of co- administration of CIM with DM. The results revealed that CIM has the ability to modulate the effects of DM and codeine on brain GABA and 5-HT contents, while it causes an increase in brain GABA and 5-HT content during its use with DP