Determination of acute oral toxicity of tetrahydropyridone and hexahydroquinoline individual derivatives, derivatives of α-cyanothioacetamide

The relevance of this study is due to the high number of side effects caused by nonsteroidal anti-inflammatory drugs. Our previous studies consecrated anti-inflammatory, antipyretic and analgesic bioactivity of tetrahydropyridines and hexahydroquinolines, derivatives of α-cyanothioacetamide. 

Objective. The objective was to determine the acute oral toxicity in vivo of new tetrahydropyridine and hexahydroquinoline derivatives, derivatives of α-cyanothioacetamide, with laboratory codes ТD0364, ТD0353, ТD0351, CV036, CV125 and OC05184. 

Materials and methods. The study was conducted in accordance with the Interstate standard GOST 32644-2014 (OECD, Test No. 423:2001, IDT) on 63 white laboratory female rats weighing 180-220 g in autumn in a certified pharmaceutical laboratory. 

Results. The introduction of five prototypes of tetrahydropyridine and hexahydroquinoline derivatives in the maximum (2,000 mg/kg) dosage under laboratory codes ТD0364, ТD0353, ТD0351, CV036, CV125 was characterized by zero mortality. We have discovered no visible signs of neurotoxicity, ulcerogenic properties, and hepatotoxicity. Intragastric administration of the compound OC 05184 in a dose of 2,000 mg/kg caused death of all rats in the group within the first 12 hours; however, the introduction of the sample OC 05184 in the dosage of 300 mg/kg did not lead to death for 2 weeks. Moreover, there were no signs of toxicity from the first minute of intragastric administration. 

Conclusion. Five of the investigated tetrahydropyridine and hexahydroquinoline derivatives coded ТD0364, ТD0353, ТD0351, CV036 and CV125 belong to low toxic compounds (5th toxicity grade). The compound with the laboratory code 05184 OC belongs to the 4th toxicity class.