Safety of Nivalin (Galantamine). Toxicity studies!



Primary toxic effect and acute toxicity of Nivalin

The toxic effects of Nivalin have been studied in animals: frogs, albino mice, albino rats, rabbits and cats. The common primary toxic effect is increased reflex activity, appearance of clonic-tonic seizures, muscle twitches, intense salivation, increased rate of breathing (tachipnoea). These symptoms intensify with dose increase and test animals die in convulsion and asphyxia. The symptoms are analogous to those caused by other known anticholinesterase drugs, the difference being quantitative and dose-dependent. Experiments in cats showed more prominent M-cholinergic effects in comparison with other species where M-cholinergic effects dominated.

Quantitatively, the toxic doses of Nivalin for experimental animals are considerably higher than those of neostigmine, table 1.

Table 1. Comparative data for LD50 of Nivalin and LD50 of Neostigmine

Test animal Nivalin mg/kg Neostigmine mg/kg
p.o. s.c. i.v. p.o. s.c. i.v.
Mice 24 24-25 3.8-5.5 14.4 0.4-0.6 0.315-0.36
Rats 75-79.43 52-75 11.2 - - -
Rabbits 75 27 LD1009-12 - 0.5-0.75 0.2

Chronic toxicity of Nivalin

Chronic toxicity studies of Nivalin employed repeated oral doses of 0.25, 0.50, 10.00 mg/kg body weight and subcutaneously dose of 0.125, 0.25, 05 mg/kg for six months in sexually mature Wistar rats. Throughout the trial period, no deviations from the normal biometric, haematologic, and morphologic parameters were observed in the treated animals. Pregnancy and labor proceeded normally. No statistically significant differences were found in comparison with the control group, except increased motor activity for about 2 h following the administration of higher doses. The doses used in those studies are equivalent to the mean therapeutic daily dose for humans, used in single and divided (twice and four times daily) intake.

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