Inhibition by Norakin (triperiden) of Sindbis virus infection in mice

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.