Abstract
Twelve adult Collie dogs were studied to determine the effects of ivermectin on neurotransmitter metabolites released from the brain into the cerebrospinal fluid (CSF) and on CSF pressure. Ten of the 12 Collies were given ivermectin orally at a concentration of 200 μg/kg body weight. Three of these 10 Collies showed clinical signs of ivermectin-induced toxicosis which progressed into a state of unresponsive recumbency in 2 dogs.
Cerebrospinal fluid pressures and neurotransmitter metabolite concentrations in cisterna magna CSF were analysed 49 to 50 hours after administration of ivermectin in 6 of the 10 treated dogs, and in the 2 untreated control Collies. Cerebrospinal fluid pressures were within normal limits in all dogs. However, compared to the CSF concentrations in the 2 untreated and 3 non-reactive Collies, the 2 ivermectin-reactive Collies still in recumbency had elevated CSF concentrations of homovanillic acid (HVA), a metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin. These findings suggest an association between altered neurotransmission and severe ivermectin-induced neurological abnormalities. No evidence of elevated intracranial pressure was found.
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References
Bartholini, G. 1980. Interaction of striatal dopaminergic, cholinergic and GABAergic neurons: relation to extrapyramidal function. Trends in Pharmacological Science, 6, 138–140
Bennett, D.G. 1986. Clinical pharmacology of ivermectin. Journal of the American Veterinary Medical Association, 189, 100–104
Borg, J., Warter, J.M., Schlienger, J.L., Imler, M., Marescaux, C. and Mack, G., 1982. Neurotransmitter modifications in human cerebrospinal fluid and serum during hepatic encephalopathy. Journal of Neurological Science, 57, (2), 343–356
Campbell, W.C. 1981. An introduction to the avermectins. New Zealand Veterinary Journal, 29, 174–178
Campbell, W.C., Fisher, M.H., Stapley, E.O. et al. 1983. Ivermectin: a potent new antiparasitic agent. Science, 221, 823–828
Chesselet, M.F. 1984. Commentary: presynaptic regulation of neurotransmitter release in the brain. Neuroscience, 12, 347–375
Cooper, J.R., Bloom, F.E. and Roth, R.H. 1986. In: The Biochemical Basis of Neuropharmacology, 5th Edn., (Oxford University Press, New York), 203–314
Costa, E. and Meek, J.L. 1974. Regulation of biosynthesis of catecholamines and serotonin in the CNS. Annual Review of Pharmacology, 14, 491–511
Enna, S.J. 1981. GABA receptor pharmacology: functional considerations. Biochemical Pharmacology, 30, 907–913
Herrera-Marschitz, M. and Ungerstedt, U. 1987. The dopamine-γ-aminobutyric acid interaction in the striatum of the rat is differently regulated by dopamine D-1 and D-2 types of receptor: evidence obtained with rotational behavioural experiments. Acta Physiologica Scandinavica, 129, 371–380
McGeer, P.H., Eccles, J.C. and McGeer, E.G. 1987. In: Molecular Neurobiology of the Mammalian Brain, 2nd Edn. (Plenum Press, New York), 197–225
Mignot, E., Laude, D. and Elghozi, J.L. 1984. Kinetics of drug-induced changes in dopamine and serotonin metabolite concentrations in the CSF of the rat. Journal of Neurochemistry, 42, 819–825
Nielson, J.A. and Johnston, C.A. 1982. Rapid, concurrent analysis of dopamine, 5-hydroxytryptamine, their precursors and metabolites utilizing high performance liquid chromatography with electrochemical detection: analysis of brain tissue and cerebrospinal fluid. Life Sciences, 31, 847–856
Obata, K., Ito, M., Ochi, R. and Sato, N. 1967. Pharmacological properties of the postsynaptic inhibition of Purkinje cell axons and the action of γ-aminobutyric acid on Deiters' neurons. Experimental Brain Research, 4, 43–57
Palfreyman, M.G., Hout, S. and Wagner, J. 1982. Value of monoamine metabolite determinations in CSF as an index of their concentrations in rat brain following various pharmacological manipulations. Journal of Pharmacological Methods, 8, 183–196
Paul, A.J., Tranquilli, W.J., Seward, R.L., Todd, K.S. and DiPietro, J.A. 1987. Clinical observations in Collies given ivermectin orally. American Journal of Veterinary Research, 8 (4), 684–685
Pong, S.S., Wang, C.C. and Fritz, L.C. 1980. Studies on the mechanism of action of avermectin B a: stimulation of release of γ-aminobutyric acid from brain synaptosomes. Journal of Neurochemistry, 34, 351–358
Pulliam, J.D., Seward, R.L., Henery, R.T. and Steinberg, S.A. 1985. Investigating ivermectin toxicity in Collies. Veterinary Medicine, 80, 33–40
Sharman, D.F. 1981. The turnover of catecholamines In: C.T.Pylock and P.V.Taberner (eds.), Central Neurotransmitter Turnover, (University Park Press, Baltimore), 20–58
ShepardG.M. 1988. Synaptic potentials and synaptic integration. In: Neurobiology, 2nd Edn., (Oxford University Press, New York), 122–144
SimpsonS.T. and ReedR.R. 1987. Manometric values for normal cerebrospinal fluid pressure in dogs. Journal of the American Animal Hospital Association, 23, 629–632
SivamS.P., HudsonP.M., TilsonH.A. and HongJ.S. 1987. GABA and dopamine interaction in the basal ganglia: dopaminergic supersensitivity following chronic elevation of brain γ-aminobutyric acid levels. Brain Research, 412, 29–35
VaughnD.M., ColemanE., SimpsonS.T. and SatjawatcharaphongC. 1988. Analysis of neurotransmitter metabolite concentrations in canine cerebrospinal fluid. American Journal of Veterinary Research, 49 (8), 1302–1306
ZukerR.S. 1987. Neurotransmitter release and its modulation. In: L.K.Kaczmarek and I.B.Levitan (eds.), Neuromodulation: The Biochemical Control of Neuronal Excitability, (Oxford University Press, New York), 243–263
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Vaughn, D.M., Simpson, S.T., Blagburn, B.L. et al. Determination of homovanillic acid, 5-hydroxyindoleacetic acid and pressure in the cerebrospinal fluid of Collie dogs following administration of ivermectin. Veterinary Research Communications 13, 47–55 (1989). https://doi.org/10.1007/BF00366852
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DOI: https://doi.org/10.1007/BF00366852