Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Droxidopa”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1987

Studies on the activity of L-threo-3,4-dihydroxyphenylserine (L-DOPS) as a catecholamine precursor in the brain. Comparison with that of L-dopa.

L-Threo-3,4-dihydroxyphenylserine (L-DOPS) was compared with L-3,4-dihydroxyphenylalanine (L-DOPA) with respect to their activities as central amine precursors. The apparent Km value (the substrate affinity) of L-DOPS for aromatic L-amino acid decarboxylase was nearly equal to that of L-DOPA, whereas the vmax value (the rate of decarboxylation) of L-DOPS was much smaller than that of L-DOPA, the penetration of L-DOPS into the brain through the blood-brain barrier was found to be smaller (about one-fourth) than that of L-DOPA but, for an amine precursor, it was still substantial. Unlike L-DOPA, L-DOPS did not cause a marked accumulation of norepinephrine (NE), the corresponding catecholamine in the brain, but nialamide, a monoamine oxidase inhibitor significantly enhanced the L-DOPS-induced rise of NE. Moreover, the brain concentration of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG), the principal end metabolite of NE, was increased markedly by L-DOPS. These results suggest that L-DOPS may act as an NE precursor in the brain and activate NE neurons by increasing the turnover rate of NE.

Animals↗
PubMed1986

Dopaminergic involvement in the estrogen-induced suppression of frequency of pulsatile luteinizing hormone secretion in the ovariectomized rat.

This experiment examined whether various catecholaminergic synthesis inhibitors and receptor blockers affect the inhibitory effect on the frequency of pulsatile luteinizing hormone (LH) secretion induced by local application of estradiol benzoate (EB) into the preoptic suprachiasmatic area (POSC) of ovariectomized rats. Ovariectomized rats were pretreated with either alpha-methyl-p-tyrosine (AMPT; tyrosine hydroxylase inhibitor), AMPT plus threo-dihydroxyphenylserine (DOPS; norepinephrine precursor), diethyldithiocarbamate (DDC; dopamine-beta-hydroxylase inhibitor), pimozide (dopaminergic receptor blocker), phenoxybenzamine (alpha-adrenergic receptor blocker), propranolol (beta-adrenergic receptor blocker), or their vehicles. EB implantation into the POSC reduced the frequency of existing pulsatile LH secretion in vehicle-treated rats. Pretreatment of the rat with AMPT, AMPT plus DOPS, or pimozide did not affect the basal pulsatile LH secretion but eliminated the suppressive effect of EB implantation on the LH pulse frequency. In rats pretreated with DDC or phenoxybenzamine, basal pulsatile LH secretion was significantly inhibited, and EB implantation did not lower serum LH further in these rats. Propranolol had no obvious effect on either basal pulsatile LH secretion or EB-induced suppression of LH pulse frequency. These findings suggest that, in addition to the alpha-adrenergic involvement in maintaining the basal pulsatile LH secretion, the intact dopaminergic system is required for the suppression of the frequency of LH pulses induced by estrogen.

Animals↗
PubMed1987

Effects of L-threo-DOPS, an L-noradrenaline precursor, on locus coeruleus-originating neurons in spinal trigeminal nucleus.

Electrophysiological studies using reserpinized cats were performed to examine the effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the noradrenergic pathway from the locus coeruleus (LC) to the spinal trigeminal nucleus (STN). The spike generation of STN relay neurons induced by trigeminal nerve stimulation was not affected by LC conditioning stimulation nor iontophoretic application of L-threo-DOPS. After intraventricular administration of L-threo-DOPS, the inhibition of the spike generation was seen with LC conditioning stimulation and blocked by iontophoretically applied sotalol, suggesting that L-noradrenaline converted from L-threo-DOPS inhibits transmission of STN relay neurons.

Action Potentials↗
PubMed1991

Effects of L-threo-DOPS, a noradrenaline precursor, on the long-term potentiation in the rat hippocampal mossy fiber-CA3 region.

The effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a synthetic precursor of norepinephrine (NE), on the long-term potentiation (LTP) in the hippocampal mossy fiber-CA3 system was examined in urethane-anesthetized rats, the objective being to determine whether or not this drug acts as NE on the LTP. L-threo-DOPS may be effective for treating some type of mental disorders, including dementia. The LTP, induced in CA3 by tetanic stimulation (100 Hz for 1 s) applied to the mossy fiber persisted for more than 4 h. When L-threo-DOPS (50 and 150 micrograms) was injected into the lateral ventricle 30 min prior to the tetanic stimulation, there were no significant alterations in the LTP. However, in animals treated with reserpine (5 mg/kg i.p.) 24 h before the experiment, LTP was not induced with tetanic stimulation alone yet was obtained when tetanic stimulation was preceded by L-threo-DOPS (50 and 150 micrograms) applied to the ventricle. The LTP obtained by L-threo-DOPS in the reserpine-treated animal was inhibited by pretreatment with benserazide and was completely blocked by the simultaneous administration of sotalol. These results suggest that NE converted from L-threo-DOPS plays an important role in inducing LTP in the mossy fiber-CA3 system in the animals deficient in catecholamines.

Anesthesia↗
PubMed1995

Central nervous stimulants facilitate sexual behavior in male rats with medial prefrontal cortex lesions.

Male rats with lesions of the cerebral cortex near the midline in the frontal region destroying most of the cingulate cortex and producing some damage to adjacent frontal areas have very long mount and intromission latencies. Otherwise their sexual behavior is essentially normal. The dopamine releasers amfonelic acid, 0.5 mg/kg, and amphetamine, 1 mg/kg, reduced the mount and intromission latencies in males with such lesions. Caffeine, 30 mg/kg, had similar effects. None of the drugs modified sexual behavior in intact males. It has been suggested that medial prefrontal lesions reduce the animal's reactivity to environmental stimuli, and hence renders the activation of sexual behavior difficult. Present results show that stimulant drugs are capable of compensating for this reduced reactivity. The possible mechanisms behind this effect are discussed. The lesion had also a small but consistent effect on the intromission ratio, suggesting some motor impairment. The effect on intromission ratio was not reduced by the drugs, suggesting that the lesion's motor consequences are mediated by mechanisms different from those controlling behavioral reactivity. The noradrenaline precursor dl-threo-dihydroxyphenylserine, 10 mg/kg, in combination with carbidopa, 50 mg/kg, increased mount and intromission latencies in both intact and lesioned males. Thus, activation of noradrenergic neurotransmission had effects opposite to those found after activation of dopaminergic transmission. Noradrenergic stimulation cannot, therefore, be important for the effects of amphetamine or amfonelic acid.

Amphetamine↗
PubMed1996

Depressor action of L-threo-dihydroxyphenylserine in the rat nucleus tractus solitarii.

Microinjections of L-threo-dihydroxyphenylserine (L-threo-DOPS, 0.1-3 ng), a synthetic precursor amino acid of noradrenaline, into the medial area of the nucleus tractus solitarii produced dose-dependent depressor and bradycardic responses in anesthetized rats treated with or without i.p. 3-hydroxybenzylhydrazine, a central inhibitor of L-aromatic amino acid decarboxylase. D-threo-DOPS (3 ng) produced no effect. L-Dihydroxyphenylalanine (L-DOPA) methyl ester (1 microgram), a competitive antagonist of L-DOPA, microinjected into the nucleus tractus solitarii, blocked the depressor and bradycardic responses to L-threo-DOPS itself produces vasodepressor actions without its conversion to noradrenaline, probably via a recognition site for L-DOPA in the rat nucleus tractus solitarii.

Animals↗
PubMed1986

Effect of L-threo-3,4-dihydroxyphenylserine chronic administration on cerebrospinal fluid and plasma free 3-methoxy-4-hydroxy-phenylglycol concentration in patients with Parkinson's disease.

L-Threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was administered as a means of treating akinesia in 9 patients with Parkinson's disease and one with pure akinesia. Akinetic symptoms were improved in 7 of 10 patients. During chronic L-threo-DOPS treatment, cerebrospinal fluid (CSF) and plasma concentrations of free 3-methoxy-4-hydroxyphenylglycol (MHPG) and L-threo-DOPS were measured in these 10 patients. The results show that there were no significant changes in either CSF or plasma free MHPG concentrations before or during L-threo-DOPS administration. The L-threo-DOPS concentration during treatment was not measurable in the CSF of 2 patients nor in the plasma of 1 out of 4 patients given only L-threo-DOPS. It was, however, measured in all patients treated with a combination of L-threo-DOPS and L-DOPA plus carbidopa. The results show that L-threo-DOPS is transported into the CSF, and suggest that its active mechanism may be further clarified by studying its action on not only noradrenaline, but also other neurotransmitters.

Adult↗
PubMed1988

Effect of L-threo-3,4-dihydroxyphenylserine on regional cerebral blood flow in patients with Parkinson's disease.

Regional cerebral blood flow (rCBF) was measured by the 133Xe inhalation technique in 9 patients with Parkinson's disease and in 1 patient with pure akinesia before and during treatment with L-threo-3,4-dihydroxyphenylserine (DOPS). L-DOPS alone was administered in 4 patients, and combined with L-DOPA or bromocriptine in 6 patients. The mean, hemispheric and regional CBF was unaffected by the chronic administration of L-DOPS. In addition, no significant difference in the mean CBF was observed between the patients who showed marked or moderate improvement in parkinsonian symptoms during the treatment with L-DOPS and those who showed slight improvement or no change, or between the group treated with L-DOPS alone and the group treated in combination with L-DOPS and other drugs. These results indicate that L-DOPS does not increase the CBF in parkinsonian patients, thus the anti-parkinsonian effects of the agent are not mediated by changes in CBF.

Adult↗
PubMed1985

Mass spectrometric measurements of norepinephrine synthesis in man from infusion of stable isotope-labelled L-threo-3,4-dihydroxyphenylserine.

The kinetics of stable isotope-labelled L-threo-3, 4-dihydroxyphenylserine(L-threo-DOPS), an immediate precursor of (-)-norepinephrine, was studied to investigate the pharmacologic mechanism of its therapeutic effect on orthostatic hypotension in familial amyloid polyneuropathy(FAP) and on akinesia and freezing in parkinsonism. [13C,D]-L-threo-DOPS was synthesized, and 100 mg of the compound was infused for 2 h into two normal subjects, two FAP patients and two patients with the degenerative diseases of the central nervous system. Labelled and endogenous norepinephrine in urine and plasma was assayed simultaneously by gas chromatography/mass spectrometry. The results indicate that the increase in norepinephrine in biological fluids after administration of L-threo-DOPS is attributable mostly to norepinephrine derived from L-threo-DOPS, not to pre-formed endogenous norepinephrine released by L-threo-DOPS.

Atrophy↗
PubMed1987

Effect of L-threo-3,4-dihydroxyphenylserine(L-threo-DOPS) on brain and serum MHPG levels in mice: evidence for NE formation in CNS.

Effects of L-threo-DOPS on brain and serum concentrations of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), a major metabolite of 1-norepinephrine(NE) were studied in mice. An intraperitoneal(i.p.) injection of L-threo-DOPS markedly increased both serum and brain MHPG levels in mice. This increase in the brain was dose-dependent at doses up to 800 mg/kg, and lasted for 4 h or more. Though the increase in serum total-MHPG was 3-4 times greater than that in brain MHPG, the decline was rapid as compared with the case of brain MHPG. The L-threo-DOPS-induced increase in MHPG was inhibited by i.p. pretreatment with benserazide, a peripheral decarboxylase inhibitor, in both serum and brain. This inhibition in the brain, however, was observed at about 20 times higher doses of benserazide than that in serum. On the contrary, an intracerebroventricular(i.c.v.) injection of benserazide inhibited the increase in brain MHPG to about the same degree as that in serum MHPG. These results suggest that the L-threo-DOPS-induced increase in brain MHPG is not likely to originate in peripheral organs including the brain capillary, and that L-threo-DOPS can be converted to NE by aromatic L-amino acid decarboxylase(AADC) in the brain parenchyma.

Animals↗
PubMed1987

Inhibition of monoamine oxidase by 3,4-dihydroxyphenyl L-alanine and its analogues.

L-3,4-Dihydroxyphenylalanine (DOPA) was found to inhibit type A monoamine oxidase in human placental mitochondria. The inhibition proved to be noncompetitive with the substrate, kynuramine, and the inhibition was completely reversible. D-DOPA was found to inhibit monoamine oxidase in the same way, and the apparent Ki values of L- and D-DOPA were obtained to be 154 microM and 133 microM, respectively. L-alpha-Methyl-DOPA was found to inhibit the MAO activity competitively with the substrate, but studies with other analogues of DOPA revealed that the inhibition required an amino and a carboxyl group at alpha-position. The substitution of a hydroxy group at 3 or 4 position of catechol ring with a methoxy group was found to abolish the inhibition of the MAO activity. In addition to type A MAO in human liver and placental mitochondria, type B MAO in liver mitochondria was inhibited by L-DOPA, but type B MAO was less sensitive to L-DOPA. These results were discussed in terms of its possible regulation of the level of biogenic amines in the brain.

Dihydroxyphenylalanine↗
PubMed1987

Stimulation of prolactin secretion by L-3,4-dihydroxyphenyl-serine (L-DOPS) via central norepinephrine in the rat.

Intracerebroventricular (icv) injection of L-3,4-dihydroxyphenylserine (L-DOPS) (50 and 250 micrograms/rat) raised in a dose-related manner both plasma prolactin (PRL) and CSF norepinephrine (NE) in urethane-anesthetized male rats. Intravenous (iv) injection of larger doses of L-DOPS (5 and 10 mg/100 g BW) slightly but significantly increased plasma PRL and CSF NE. L-DOPS injection (50 micrograms/rat, icv or 5 mg/100 g BW, iv) also raised plasma PRL in conscious rats. There was a good correlation (r = 0.74) between CSF NE and peak plasma PRL in the anesthetized animals. Propranolol (100 micrograms/100 g BW, iv) inhibited plasma PRL responses to L-DOPS (50 micrograms/rat, icv) and NE injection (1 microgram/rat, icv) raised plasma PRL in anesthetized animals. These findings indicate that L-DOPS stimulates PRL secretion via central noradrenergic mechanisms in the rat.

Animals↗
PubMed1987

Catecholaminergic control of plasma growth hormone and thyrotropin levels in hypophysectomized rats bearing ectopic pituitary transplants.

Transplantation of the anterior pituitary to an ectopic site leads to stimulation of PRL secretion and suppression of the release of other adenohypophyseal hormones. We have previously reported that precursors and blockers of catecholamine synthesis can affect PRL release from the ectopic pituitary. In the present study we have measured the effects of L-3,4-dihydroxyphenylalanine (DOPA), DL-threo-dihydroxyphenylserine (DOPS), alpha-methyl-para-tyrosine (alpha-mpt) and diethyldithiocarbamate (ddc) on plasma growth hormone (GH) and thyrotropin (TSH) levels in hypophysectomized rats with pituitary transplants under the renal capsule. In these animals, peripheral plasma GH levels were elevated by a precursor (DOPA) and reduced by a blocker (alpha-mpt) of catecholamine synthesis. Plasma TSH levels were increased by a precursor (DOPS) and reduced by a blocker (ddc) of norepinephrine synthesis. We suspect that GH and TSH present in the circulation of pituitary-grafted animals were derived, in part, from the ectopic pituitary tissue and suggest that the small but detectable secretion of hormones other than PRL in this animal model is under the control of endogenous catecholamines.

Animals↗
PubMed1988

Increase in norepinephrine turnover after tyrosine or DL-threo-3,4-dihydroxyphenylserine (DL-threo-DOPS).

The amino acids tyrosine and DL-threo-3,4-dihydroxyphenylserine (DL-threo-DOPS) were compared for their effectiveness in increasing central nervous system norepinephrine (NE) turnover in both saline and DSP-4 pretreated mice. NE was decreased significantly in cortex, hippocampus and cerebellum, and only slightly in hypothalamus and brainstem two weeks after a single intraperitoneal injection of the neurotoxin DSP-4. Levels of the major NE metabolite, 3-methoxyl-4-hydroxyphenylethylene glycol (MHPG), decreased in parallel in these five brain regions. Neither administration of tyrosine (250 mg/kg, as the ethyl ester, i.p.) nor DL-threo-DOPS (200 mg/kg, i.p.) affected regional NE concentration. However, after tyrosine administration, MHPG levels increased significantly in cortex in control mice and in cortex and hippocampus of DSP-4 pretreated mice. In all five brain noradrenergic regions MHPG level increased after DL-threo-DOPS administration and this increase was enhanced (approximately doubled) in DSP-4 pretreated mice. Thus, both amino acids may be useful as precursors of central NE when its level is depleted (e.g. following administration of DSP-4); DL-threo-DOPS producing a generalized increase in brain NE turnover, while increases following tyrosine are specific to those areas in which neuronal activity is increased i.e. cortex and hippocampus.

Animals↗
PubMed1976

DDC-induced retrograde amnesias prevented by injections of dl-DOPS.

Injection of a dopamine beta-hydroxylate inhibitor, diethyldithiocarbamate (DDC) in rats 30 min prior to training of a step-down passive avoidance task impaired performance of the task 24 hr later. Similarly, injection of DDC 30 min prior to testing blocked retrieval of a passive avoidance habit trained in normal rats the previous day. Injection of a direct norepinephrine (NE) precursor, dl-thero 3,4-dihydroxyphenylserine (DOPS) 60 min before DDC prevented both amnesias. These data support the hypothesis that reduced levels of NE are responsible for DDC-induced amnesias.

Amnesia, Retrograde↗
PubMed1979

Significance of central noradrenergic system on harmaline induced tremor.

Since there is degeneration of substantia nigra concomitant with that of locus coeruleus (LC) in patients with Parkinson's disease, the study was performed to determine the role of central norepinephrine (NE) on harmaline induced tremor. The duration of harmaline (10 mg/kg IP) induced tremor was significantly reduced by intraventricular administration of L-thero-3,4-dihydroxyphenylserine (200 micrograms/rat) and 1-NE (50 micrograms/rat) was increased NE levels in the cerebral cortex, striatum, diencephalon, cerebellum and brain stem. Electrical stimulation of bilateral LC suppressed harmaline-induced 10-12/sec EMG activities in the neck muscle. Bilateral LC lesion upon electrocoagulation and 6-hydroxydopamine treatment resulted in a significant prolongation of the duration of harmaline induced tremor, reducing NE levels in the brain. These data suggest that central NE originating in the LC neurons has an inhibitory effect on the development of the tremor induced by harmaline.

Alkaloids↗