Intranasal (i. n.)
infection with 10 LD50 of Sindbis virus caused acute
encephalomyelitis and death in ABD2F1 mice 3-7 days post
infection (p.i.). Histologic lesions were found in the CNS, pancreas. liver, parotid glands, exorbital lacrimal glands, lymphoid organs and kidneys. Repeated
oral administration of the
anticholinergic anti-Parkinson
drug Norakin protected infected animals from death in a dose-dependent manner when treatment was started prior to but not after virus inoculation. The maximum protective effect was achieved when the
drug was administered twice daily at doses of 2.5 or 5.0 mg/kg body mass for at least 56 hr; single
injections of the full daily dose were ineffective. Daily doses of greater than or equal to 25 mg/kg body mass had a reduced protective effect or failed to prevent mortality. Administration of
Norakin up to doses of 300 mg/kg body mass per day to noninfected ABD2F1 mice were tolerated without obvious clinical or histological signs of illness over a period of 104 hr. Replication of sindbis virus in BHK 21/C13 cells was not inhibited by
Norakin concentrations up to 10 micrograms/ml. In Mengo virus-infected mice
Norakin did not exert any protective effect within the range of 1.25-50.0 mg/kg body mass when treatment started 1 hr before
infection and has been continued twice daily over a period of 104 hr.