Summary
The effect of l-threo-DOPS on the reserpine-induced ptosis in mice and its modification by imipramine, a norepinephrine (NE) uptake inhibitor, or nialamide, a monoamineoxidase inhibitor, were studied.
Intraperitoneal (i.p.) injection of l-threo-DOPS (800 mg/kg) significantly reduced the severity of the ptosis. This reversal of the ptosis by l-threo-DOPS was markedly potentiated by i.p. injection of either imipramine (2.5 mg/kg) or nialamide (30 mg/kg). Response to l-threo-DOPS was also significantly potentiated by intracerebroventricular (i.c.v.) injection of imipramine (10 μg). On the other hand, this treatment with imipramine (10 μg, i.c.v.) also significantly potentiated the reversal of the ptosis by NE (20 μg, i.c.v.), but the reversal by the subcutaneous (s.c.) injection of NE (1 and 3 mg/kg) was not affected.
Reserpine (5 mg/kg, i.p.) markedly decreased the brain content of NE in mice, whereas l-threo-DOPS (400 mg/kg, i.p.) slightly restored it. Moreover, by the pretreatment with nialamide (30 mg/kg, i.p.), l-threo-DOPS produced a significant increase in the brain content of NE in reserpinetreated mice.
These results suggested that l-threo-DOPS was capable of reversing the reserpine-induced ptosis due to the formation, at least in part of (−)-NE at the synaptic sites of central noradrenergic neurons.
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References
Ahlenius S, Engel J (1973) Antagonism by dl-threo-DOPS of suppression of a conditioned avoidance response induced by a dopamine-β-hydroxylase inhibitor. J Neural Transm 34:267–277
Bartholini G, Constantinidis J, Puig M, Tissot R, Pletscher A (1975) The stereoisomers of 3,4-dihydroxyphenylserine as precursor of norepinephrine. J Pharmacol Exp Ther 193:523–533
Bernheimer H, Birkmayer W, Hornykiewicz O (1963) Zur Biochemie des Parkinson-Syndroms des Menschen. Einfluß der Monoaminoxydase-Hemmer-Therapie auf die Konzentration des Dopamins, Noradrenalin und 5-Hydroxytryptamins im Gehirn. Klin Wochenschr 41:465–469
Carlsson A, Lindqvist M, Magnusson T (1957) 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180:1200
Creveling CR, Daly J, Tokuyama T, Witkop B (1968) The combined use of alpha-methyltyrosine and threo-dihydroxyphenylserine. Selective reduction of dopamine levels in the nervous system. Biochem Pharmacol 17:65–70
Fujiwara H, Inagaki C, Ikeda Y, Tanaka C (1976) Decarboxylation of steroisomers of 3,4-dihydroxyphenylserine (DOPS) in mice. Folia Pharmacol Jpn 72:891–898
Haley TJ, McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol 12:12–15
Holzbauer M, Vogt M (1956) Depression by reserpine of norepinephrine concentration in the hypothalamus of the cat. J Neurochem 1:8–11
Inagaki C, Fujiwara H, Tanaka C (1976) Inhibitory effect of (+)threo-3,4-dihydroxyphenylserine (DOPS) on decarboxylase of (−)threo-DOPS. Jpn J Pharmacol 26:380–382
Iversen LL (1965) Inhibition of norepinephrine uptake by drugs. J Pharm Pharmacol 17:62–64
Nagatsu T, Kato T, Numata Y, Ikuta K, Sano M, Nagatsu I, Kondo Y, Inagaki S, Izuka R, Hori A, Narabayashi H (1977) Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain. Clin Chem Acta 75:221–232
Nakamura M, Fukushima H (1976) The effect of tricyclic antidepressant and neuroleptics on the peripheral and central action of norepinephrine in reserpine-treated mice. Eur J Pharmacol 38:343–348
Narabayashi H, Kondo T, Hayashi A, Suzuki T, Nagatsu T (1981) l-threo-3,4-Dihydroxyphenylserine treatment for akinesia and freezing of Parkinsonism. Pro Jpn Acad 57 (Ser. B):351–354
Ohmura I, Inagaki C, Araki H, Tanaka C (1978) Enzymatic decarboxylation of l-threo-3,4-dihydroxyphenylserine in rat heart. Jpn J Pharmacol 28:747–753
Porter CC, Torchiana ML, Stone CA (1972) (S)-Norepinephrine in the tissues of mice and rats gived racemic erythro-3,4-dihydroxyphenylserine (DOPS). Life Science Part I, Physiol Pharmacol 11:787–795
Refshauge C, Kissinger PT, Dreiling R, Blank L, Freeman R, Adams RN (1974) New high performance liquid chromatographic analysis of brain catecholamines. Life Science 14:311–321
Riezen HV, Delver A (1971) The effect of a number of drugs with different pharmacological properties upon reserpine induced hypothermia in mice. Arzneim-Forsch 21 (10):1562–1566
Sano Y, Hirai M, Matsuoka M, Nakajima T (1973) 3,4-Dihydroxyphenylserine as a norepinephrine precursor. Sinkeikagaku (in Japanese) 12:96–98
Shore PA (1962) Release of serotonin an catecholamines by drugs. Pharmacol Rev 14:531–550
Suzuki T, Higa S, Sakoda S, Hayashi A, Yamamura Y, Takabe Y, Nakajima A (1981) Orthostatic hypotension in familial amyloid polyneuropathy. Treatment with dl-3,4-dihydroxyphenylserine. Neurology 31:1323–1326
Suzuki T, Higa S, Sakoda S, Ueji M, Hayashi A, Takada Y, Nakajima A (1982) Pharmacokinetic studies of oral l-threo-3,4-dihydroxyphenylserine in normal subjects and patients with familial amyloid polyneuropathy. Eur J Clin Pharmacol 23:463–468
Svensson TH (1971) On the role of central noradrenaline in the regulation of motor activity and body temperature in the mouse. Naunyn-Schmiedeberg's Arch Pharmacol 271:111–120
Yamazaki M, Ikeda Y, Ishikawa M, Tanaka C (1976) Inhibition of harmaline tremor induced by l-threo-3,4-dihydroxyphenyl-serine, a norepinephrine precursor. Folia Pharmacol Jpn 72:363–369
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Kato, T., Katsuyama, M., Karai, N. et al. Reversal of the reserpine-induced ptosis by l-threo-3,4-dihydroxy-phenylserine (l-threo-DOPS), a (−)-norepinephrine precursor, and its potentiation by imipramine or nialamide. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 243–246 (1986). https://doi.org/10.1007/BF00504861
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DOI: https://doi.org/10.1007/BF00504861