The effect of cinanserin (antiserotonin agent) on canine renal allografts

Abstract

A new compound, cinanserin, which possesses antiserotonin as well as immunosuppressive properties, was tested in dog renal allografts. Increased survival rates were noted a t a dose level of 40 mg/kg/day. Increasing drug therapy above this level was associated with hepatotoxicity. There was no evidence of bone marrow toxicity. Histologically, characteristic features of allograft rejection were generally unmodified. Serological alterations seen in untreated renal allografts were generally suppressed t o a limited degree.

Cinanserin Is an Inhibitor of the 3C-Like Proteinase of Severe Acute Respiratory Syndrome Coronavirus and Strongly Reduces Virus Replication In Vitro

“…It had been synthesized and characterized as a serotonin inhibitor by The Squibb Institute for Medical Research, New Brunswick, New Jersey, in the 1960s (40). Antiserotonin effects in peripheral organs, effects on the central nervous system (12,40), and immunosuppressive (1,27,35) and antiphlogistic (41) activity were demonstrated in laboratory animals. In dogs, the main side effect was hepatotoxicity at repeated oral doses of Ͼ40 mg/kg of body weight per day (35), and the lethal dose was 100 mg/kg upon intravenous infusion of the drug at a rate of 0.5 mg/kg per minute (40).…”

“…Antiserotonin effects in peripheral organs, effects on the central nervous system (12,40), and immunosuppressive (1,27,35) and antiphlogistic (41) activity were demonstrated in laboratory animals. In dogs, the main side effect was hepatotoxicity at repeated oral doses of Ͼ40 mg/kg of body weight per day (35), and the lethal dose was 100 mg/kg upon intravenous infusion of the drug at a rate of 0.5 mg/kg per minute (40). Small-scale clinical trials have been performed with patients with psychiatric disorders such as schizophrenia and mania (13,18,20,24) and in patients with carcinoid syndrome (33).…”