Possible pharmacodynamic interactions between the CNS stimulant [Nikethamide] and analgesic drugs in experimental animals

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

Modulation of the antiepileptic activity of sodium valproate by lithium chloride against pentylene-tetrazole and strychnine-indced seizures in mice.

In this study, the influence of lithium chloride [LiCl] in a dose of 10 mg/kg on the anticonvulsant activity of sodium valproate [VAL] in doses of 200 or 600 mg/kg was valuated against both pentylenetetrazol [PTZ; 100 mg/kg] and strychnine [ST; 1 mg/kg]-induced seizures and mortality. The results revealed that the ip administration of VAL alone was effective against seizures and mortality induced by both PTZ and ST. Significant increases in the onset of seizures and the MST as well as the percent of mice protected from death were recorded. In contrast, the administration of LiCl alone significantly reduced the onset of seizures and offered no protection against death caused by the same convulsive agents, PTZ and ST. Compared with valproate- treated mice, combination of lithium chloride and valproate led to a reduction in the MST of mice and an increase in the percent of protection of animals treated with PTZ and an increase in the MST of mice as well as the percent of protection in the ST- treated group of mice. Also, the results revealed that the combined administration of LiCl and VAL into mice subjected to the test convulsive agents resulted in reduced serum and brain concentration of electrolytes in FTZ-treated animals. Also, significant lowering only in the brain Na+, K+ and Cd2+ contents was observed in mice treated with ST