The effect of ketamine and its combination with indol-2-carboxylic acid and caroverine on survival time of mice with experimental tetanus

Abstract

Tetanus, also known as lockjaw, is a very dangerous infectious acute, usually afebrile disease characterized by muscle spasms, affecting humans and various animal species. The causative agent of the disease is bacteria Clostridium tetani. This bacteria produces a specific neurotoxin known as Tetanus toxin, which consists of two components: tetanospasmin and tetanolysin. Light (L) chains of tetanospamin cleavage synaptobrevin, an integral membrane component of the synaptic vesicles, which in turn prevent release of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) into the synaptic cleft. The α- motor neurons are, therefore, under no inhibitory control as a result of which they undergo sustained excitatory discharge causing the characteristic motor spasms of tetanus. In this research, we attempted to normalize the disorders caused by tetanus toxin by using ketamine, a noncompetitive antagonist of aspartate (at doses of 5, 10, 44 and 100 mg/kg of body weight – b.w.), alone and in combination with indol-2-carboxylic acid, a competitive antagonist of aspartate (at a dose of 10 mg/kg b.w.) and caroverine, a non-competitive antagonist of glutamate (at a dose of 1.2 mg/kg b.w.). Experiments were conducted on the albino mice of both sexes, weighing around 20-25 g. Experimental tetanus was induced by application of tetanus toxin. The administration of ketamine, alone and in combination with indol-2- carboxylic acid and caroverine was carried out 24 hours after administration of tetanus toxin once per day, until the mice died. It was found that ketamine had an effect only at a dose of 10 mg/kg b.w., which slightly prolonged the LD50 periodin experimental group of mice, compared to the control group of mice with experimental tetanus. Thus, it can be concluded that administration of ketamine in this dose proved to be only slightly effective. On the other hand, combination of ketamine with indol-2-carboxylic acid slightly extended the survival time of mice with experimental tetanus in the trial, as compared to the control group. Lastly, the combination of ketamine with caroverine had no effect whatsoever on the LD50period of mice with experimental tetanus.