ABSTRACT
Recently, there has been striking increase in research on drug combinations that enhance analgesia in clinical populations as well as in experimental animals. These studies involve combinations of drugs that have been viewed, as effective analgesics in their own right, such as opioids and nonsteroidal anti-inflammatory drugs, and drugs that have not traditionally been viewed as analgesics. The purpose of this study was to investigate the possible pharmacodynamic interactions between a CNS stimulant [nikethamide] and opioid [morphine] and non-opioid [paracetamol] drugs. Also, this study assessed the rationale of these interactions in terms of efficacy and safety by using different models of analgesic and behavioral tests. Albino mice and rates were used, as experimental animals. The analgesic effect of drugs and their combination was evaluated using [hot-plate] [54 °C], [tail clip] and [writhing] [acetic acid, 1%. i.p.] tests. The behavioral effects of the drugs and their combinations were also determined. Nikethamide significantly diminished the analgesic effect of morphine [1-10 mg/kg, i.p.] in all tests [antagonism] and enhanced the analgesic effect of paracetamol [50-400 mg/kg. i.p.] in all tests [additive]. Coadministration of nikethamide [100 mg/kg, i.p.] with morphine [2.71 mg/kg, ED[50]] significantly decreased locomotor activity and impaired the acquisition on conditioned avoidance responses but did not affect motor coordination to any significant extent. On the other hand, coadministration of nikethamide [100 mg/kg, i.p.] with paracetamol [117.94 mg/kg, i.p, ED[50]] significantly increased locomolor activity and improved the acquisition on conditioned avoidance responses but did not affect motor coordination to any significant extent. We can conclude that the systemic coadministration of nikethamide significantely antagonized the analgesic effect of morphine and such combination was accompanied by increased side effects. In contrast, nikethamide significantly enhanced, the analgesic effect of paracetamol in an additive fashion and this combination was not accompanied by increased side effects