The effect of haloperidol, aminooxyacetic acid and (-)-nuciferine on prolonged survival time of mice with tetanus

Abstract

Introduction. Tetanus, also known as lockjaw, is a very dangerous, infectious, acute, usually afebrile disease characterised by muscle spasms. The causative agent of the disease is the bacterium Clostridium tetani. This pathogen produces a specifc neurotoxin, termed tetanus toxin, with two components: tetanospasmin and tetanolysin. Light chains of tetanospasmin cleavage synaptobrevin, which in turn prevent release of the inhibitory neurotransmitter 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. Materials and Methods. In this research, we attempted to normalise disorders caused by tetanus toxin by using haloperidol (at doses of 4, 5, 6, 7 and 8 mg/kg b.w.), alone and in combination with (-)-nuciferine (at a dose of 5 mg/kg b.w.) or aminooxyacetic acid (at a dose of 20 mg/kg b.w.). Experiments were conducted on albino mice. Experimental tetanus was induced by application of tetanus toxin. Results and Conclusions. Application of haloperidol (alone and in combination with (-)-nuciferine and aminooxyacetic acid) was carried out 24 h following the application of tetanus toxin. It was found that haloperidol, given alone in a dose of 4 mg/kg, prolonged the average survival time of mice with experimental tetanus by 24.35 h compared to the control animals. Additionally, the combination of haloperidol with (-)-nuciferine slightly, but non-signifcantly, extended survival time , while the combination of haloperidol with aminooxyacetic acid produced the best effect on extension of survival time (mice survived on average 27.74 h longer than control mice).

Uvod. Tetanus je veoma opasna, akutna, obično afebrilna bolest koju karakteriše mišićni spazam. Uzročnik obolenja je bakterija Clostridium tetani, koja proizvodi specifčan neurotoksin ili tetanus toksin. Toksin se sastoji od dve komponente: tetanospazmina i tetanolizina. Laki lanac tetanospazmina cepa sinaptobrevin, što za posledicu ima sprečavanje oslobađanje inhibitornog neurotransmitera GABA u sinaptički procep. Funkcija ekscitatornih neurotransmitera ostaje očuvana, te pod njihovim uticajem dolazi do grča skeletne muskulature. Materijali i metode. U ovom istraživanju pokušali smo normalizovati poremećaje uzrokovane tetanus toksinom koristeći haloperidol (u dozama od 4, 5, 6, 7 i 8 mg/ kg t.m.), samostalno i u kombinaciji sa (-)-nuciferinom (u dozi od 5 mg/kg t.m.) i aminooksirćetnom kiselinom (u dozi od 20 mg/kg t.m.). Kompletno istraživanje je sprovedeno na albino miševima. Eksperimentalni tetanus izazvan je aplikacijom tetanus toksina. Rezultati i zaključak. Primena haloperidola (samo i u kombinaciji sa (-)-nuciferinom i aminooksirćetnom kiselinom) vršena je 24 sata nakon aplikacije tetanus toksina. Haloperidol, aplikovan u dozi od 4 mg/kg t.m., produžio je vreme preživljavanja miševa s eksperimentalnim tetanusom za oko 24.35 sati u odnosu na kontrolnu grupu životinja, te smo ovu dozu smatrali jedino opravdanom za dalja istraživanja. Kombinacija haloperidola s (-)-nuciferinom neznatno produžava vreme preživljavanja, dok je kombinacija haloperidola sa aminooksirćetnom kiselinom imala nabolji efekt na produženje ovog perioda. Period preživljavanja je produžen oko 27.74 sata u odnosu na kontrolnu grupu životinja.