Searching the neurotoxic effects of clonidine is one of adjuvant analgesic drug

SUMMARYThe agents used intrathecally in anaesthesiology can induce histopathologiclesions and regional haemodynamic alterations for neurons. There are numerouscauses of neurologic lesions, including direct trauma of the spinal cord and nerveroots during puncture or catheter insertion, reduced spinal cord perfusion and mostimportantly direct neurotoxic effect. Histopathologic lesions are localized either inmeninges or in neuraxis such as myelitis or axonal degeneration. Neurotoxicity canresult from decrease in neuronal blood supply, elicited by high concentrations of thesolutions, long duration exposure to local anaesthetics, and the use of adjuvants.Clonidine, an alpha 2-adrenergic drug as adjuvant with high selectivity has beenused in clinical practice for more than 20 years. It exhibits anxiolytic, sedative andanalgesic effects and also haemodynamic stabilising properties. The identification ofalpha 2-adrenoceptors has yielded information on their biochemical properties, signaltransduction, modulation of the sympathetic nervous system and neurotransmission.There is no report of neurotoxicity neither in animal studies, nor in humans, usingclonidine.The possible neurotoxicity of clonidine was studied in neuronal cells from ratneuroblastoma cell line in vitro. In this study, Cells differentiated by 24 hourstreatment with 1 mM dbcAMP, which induces outgrowth of axonal neurites. Cellviability was measured by MTT and neurite inhibition was calculate by neurotoxicityscreen test.We treated NB2a neuroblastoma cells with clonidine (Catapres) which werediluted to 1:1, 1:5 and 1:25 concentration. There was no obvious but slight toxiceffect at all selected time intervals during culture period. In the presence of anyconcentration of clonidine, toxic effect did not significantly inhibite the outgrowth ofneurites from differentiating NB2a neuroblastoma cells. However, there was dosedependent cell death according to MTT measurements and neurite inhibitionaccording to neurotoxicity screen test measurements before and after differentiationof the cells in culture. Moreover, high density cultures were more protective this slightbut not significant toxic effect.İn this study, we used neurotoxicity screen test to understand the neurotoxiceffect of clonidine without any complication of in vivo condition. The slight effect ofneurotoxicity may originate from preservation agents in the drug even clonidine may1show neuroptotective effect for them. Investigating the toxic effects on the neuronsthat are deprived from the protection of their environment in vivo conditions by usingthis method, can be important to show both the acute and late effects. As the result ofthis study, the administration of new compounds to neuron life must be supported bydata of neurotoxicity screen test and the lack of neurotoxicity must have beenpreviously checked before clinical administration.2