Summary
Bifemelane hydrochloride (bifemelane), idebenone and indeloxazine hydrochloride (indeloxazine) are used clinically to reduce apathy and other emotional disturbances in patients with cerebrovascular disease. In gerbil brains, ischemia affects many monoaminergic neurotransmitters and their metabolites. In the present study, the effects of treatment with bifemelane, idebenone and indeloxazine on ischemia-induced changes in monoamines and their metabolites were studied in ischemi gerbil brains. Although these drugs had no effect on the monoaminergic neurotransmitters or their metabolites in sham-operated animals, in the ischemi brains both dopamine and serotonin turnovers were abnormal after idebenone or indeloxazine treatment. Bifemelane, in contrast, tended to correct the ischemia-induced changes in the dopaminergic and serotonergic systems in the cerebral cortex, hippocampus and thalamus + midbrain. From the present results and those in previous reports, we conclude that bifemelane is more appropriate than idebenone or indeloxazine as a treatment for the ischemia-induced changes in monoaminergic neurotransmitter systems.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Cvejic V, Micic DV, Djuricic BM, Mrsulja BJ, Mrsulja BB (1980) Monamines and related enzymes in cerebral cortex and basal ganglia following transient ischemia in gerbils. Acta Neuropathol (Berl) 51: 71–77
Egawa M, Mitsuka M, Uemezu K, Tobe A (1984) Effects of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016) on survival time and brain monoamine levels in bilaterally carotid-artery-ligated gerbils. Jpn J Pharmacol 34: 363–365
Glowinski J, Iversen L (1966) Regional studies of catecholamines in the rat brain I. J Neurochem 13: 655–669
Haba K, Ogawa N, Mori A (1990) The effects of Sho-saiko-to-go-keishika-shakuyaku-to (TJ-960) on ischemia-induced changes of brain acetylcholine and monamine levels in gerbils. Neurochem Res 15: 487–493
Harrison MJG, Ellam LD (1981) Role of 5 HT in the morbidity of cerebral infarction-a study in the gerbil stroke model. J Neurol Neurosurg Psychiatry 44: 140–143
Hoffmeister F, Benz U, Heise A, Krause HP, Neuser V (1982) Behavioral effects of nimodipine in animals. Arzneimittelforschung 32: 347–360
Itakura T, Ueno IH, Okuno T, Komai N (1988) Protective effect of bifemelane on cortical neurons during cerebral ischemia: immunohistological study. Jpn Pharmacol Ther 16: 3101–3109
Kahn K (1972) The natural course of experimental cerebral infarction in the gerbil. Neurology 22: 510–515
Kakihana M, Yamazaki N, Nagaoka A (1984) Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia. Jpn J Pharmacol 36: 357–363
Kobayashi M, Lust WD, Passonnean JV (1977) Concentration of energy metabolites and cyclic nucleotides during and after bilateral ischemia in the gerbil cerebral cortex. J Neurochem 29: 53–59
Lastey SM, Michaelson IA, Greenland RD, McGinnis PM (1984) Simultaneous measurement of tyrosine, tryptophan and related monoamines for determination of neurotransmitter turnover in discrete rat brain regions by liquid chromatography with electrochemical detection. J Chromatogr 305: 27–42
Levy DE, Duffy TE (1975) Cerebral energy metabolism during transient ischemia and recovery in the gerbils. J Neurochem 28: 63–70
Liu J, Ogawa N, Wang X, Mori A (1991) Free radical scavenging by bifemelane hydrochloride and its major metabolites. Arch Int Pharamacodyn Ther 311: 177–187
Lust WD, Mrsulja BB, Mrsulja BJ, Passonneau JV, Klatzo I (1975) Putative neurotransmitters and cyclic nucleotides in prolonged ischemia of the cerebral cortex. Brain Res 98: 394–399
Lust WD, Arai H, Yasumoto Y, Whittingham TS, Djuricic B, Mrsulja JV, Passonneau JV (1985) Ischemic encephalopathy. In: McCandless DW (ed) Cerebral energy metabolism and metabolic encephalopathy. Plenum Press, New York, pp 79–1172
Miyazaki M, Utsumi K, Sato J (1989) Mechanisms responsible for long-term survival of adult rat hepatocytes in the presence of phenobarbital in primary culture. Exp Cell Res 182: 415–424
Nagai T, Egashira T, Yamanaka Y (1987) Effect of bifemelane hydrochloride on an injury of the liver caused by ischemia-reperfusion in rats. Jpn J Pharmacol 52: 383–385
Ogawa N, Haba K, Sora HY, Higashida A, Sato H, Ogawa S (1988a) Comparison of the effects of bifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance. Clin Ther 10: 704–711
Ogawa N, Haba K, Yoshikawa H, Ono T, Mizukawa K (1988b) Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemiainduced depletion of brain acetylcholine levels in gerbils. Res Commun Chem Pathol Pharmacol 61: 285–288
Ogawa N, Haba K, Yoshikawa H, Kawata M, Sato H (1989) Effects of lisuride hydrogen maleate on ischemia-induced depletion of brain acetylcholine levels in gerbils. Clin Ther 11: 241–246
Ohara K, Motoyasu A, Fukazawa H, Mizumo A, Taniyama J, Shiozaki K, Tamefusa N, Nishimura N, Matsumoto H, Sugitani T, Nishimoto M (1989) Clinical efficacy of bifemelane hydrochloride on cerebrovascular disease and senile dementia. Geriat Med 27: 1515–1535
Rossignol P, Margaret EI (1980) Drugs against hypoxia. Trends Pharmacol Sci 1: 287–289
Saito K, Honda S, Tobe A, Yanagiya I (1985) Effects of bifemelane hydrochloride (MCI-2016) on acetylcholine level reduced by scopolamine, hypoxia and ischemia in the rats and mongolian gerbils. Jpn J Pharmacol 38: 375–380
Scisjo BK (1981) Cell damage in the brain: a speculative syntheses. J Cereb Blood Flow Metab 1: 155–185
Scisjo BK, Wieloch T (1985) Cerebral metabolism in ischaemia: neurochemical basis for therapy. Br J Anaesth 57: 47–62
Slivka A, Brannan TS, Weinberger J, Knott PJ, Cohen G (1988) Increase in extracellular dopamine in the striatum during cerebral ischemia: a study utilizing cerebral microdialysis. J Neurochem 50: 1714–1718
Tachikawa S, Harada M, Maeno H (1979) Pharmacological and biochemical studies on a new compound, 2-(7-indenyloxy-methyl) morpholine hydrochloride (YM 08054-1), and its derivatives with potential antidepressant properties. Arch Int Pharmacodyn Ther 238: 81–95
Tobe A, Egawa M, Nagai R (1983) Effect of 7-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016) on the scopolamine-induced deficit of spontaneous alternation behavior in rats. Jpn J Pharmacol 33: 775–784
Weinberger J, Nieves-Rosa J, Cohen G (1985) Nerve terminal damage in cerebral ischemia: protective effect of brain dopamine following experimental cerebral ischemia. Nature 274: 283–284
Wurtman RJ, Zervas NT (1974) Monoamine neurotransmitters and the pathophysiology of stroke and central nervous system trauma. J Neurosurg 40: 34–36
Yamamoto M, Shimizu M (1987a) Effect of indeloxazine hydrochloride (YM-08054) on anoxia. Arch Int Pharmacodyn Ther 286: 272–281
Yamamoto M, Shimizu M (1987b) Cerebral activating properties of indeloxazine hydrochloride. Neuropharmacology 26: 761–770
Yamamoto H, Utsumi T, Miyahara M, Nobori K, Terada S, Kobayashi S, Utsumi K (1985) Effect of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride) on the structure and function of biological membraned. Pharmacometrics 30: 19–29
Yamazaki N, Take Y, Nagaoka A, Nagawa Y (1984) Beneficial effect of indebenone (CV-2619) on cerebral ischemia-induced amnesia in rats. Jpn J Pharmacol 36: 349–356
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Haba, K., Ogawa, N., Asanuma, M. et al. Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemia-induced changes in brain monoamines and their metabolites in gerbils. J. Neural Transmission 88, 187–198 (1992). https://doi.org/10.1007/BF01244732
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01244732