Nivalin®
SAFETY OF NIVALIN. 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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