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At least 199 records · Page 11Linked to original sources
PubMed1976

[Inhibition of harmaline induced tremor by L-threo-3, 4-dihydroxyphenylserine, an L-norepinephrine precursor].

Effect of 3, 4-dihydroxyphenylserine (DOPS), a norepinephrine precurosr, on harmaline tremor was investigated in mice to elucidate the role of norepinephrine in the genesis of tremor. 1) Spontaneous motor activity was inhibited by L-threo-DOPS (200 mg/kg i.p.). 2) Tremor induced by harmaline (5 and 7 mg/kg i.p.) was enhanced by alpha-methyl-p-tyrosone (200 mg/kg i.p.). 3) The development and duration of tremor induced by harmaline (10 mg/kg i.p.) were inhibited significantly in a dose dependent manner by L-threo-DOPS (50, 70, 100, 150 and 200 mg/kg i.p.), but neither by D-threo-DOPS (200 mg/kg i.p.) nor DL-erythro-DOPS (200 mg/kg i.p.). 4) L-threo-DOPS (200 mg/kg i.-.) had no effect on the development of tremor induced by tremorine (5 and 10 mg/kg i.p.), while lacrimation and diarrhea caused by tremorine was markedly inhibited. 5) Administration of harmaline (10 mg/kg i.p.) produced an increase in brain 5-hydroxytryptamine content but not in that of norepinephrine. Administration of L-threo-DOPS (100 mg/kg i.p.) increased the norepinephrine content but not the 5-hydroxytryptamine content in the brain. Inhibition of harmaline tremor induced by L-threo-DOPS is attributed to the L-norepinephrine converted from L-threo-DOPS and the involvement of a noradrenergic mechanism in harmaline tremor has to be considered.

Alkaloids↗
PubMed1976

Studies of connections between locus coeruleus and cerebral cortex.

Small tracking electrodes were inserted into the cat locus coeruleus (LC), and the effects of LC stimulation were determined on the transcallosal potential (TCP) evoked in cerebral cortex on the same side. LC stimulation at 8 volts inhibited TCP amplitude an average of 11%. Rostral LC placements appeared most effective. LC stimulation, without drugs, did not affect the peak latency of the TCP. dl-Propranolol and FLA-63 blocked LC inhibition of the TCP and also increased TCP amplitude per se. Propranolol first increased the latency of the TCP during LC stimulation, then decreased decreased it, while also prolonging the latency of the TCP per se. Phenoxybenzamine increased rather than blocked the LC inhibitory effect and also increased TCP amplitude. dl-Erythro-DOPS slightly increased the LC inhibitory effect, and substantially increased TCP amplitude. dl-Threo-DOPS produced somnolence in unanesthetized animals, led to increased norepinephrine levels in cortex and brain stem, and caused cortical potentials to fluctuate widely. A midbrain lesion of the dorsal ascending NE bundle blocked the LC inhibitory effect. LC stimulation alone, or in combination with evoked cortical stimulation, did not affect the interstimulus electrocorticogram or the heart rate. In the transcallosal system of the cortical regions studied, the LC appears to play mainly an inhibitory role.

Animals↗
PubMed1978

Enzymatic decarboxylation of L-threo-3,4-dihydroxyphenylserine in rat heart.

Decarboxylation of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) by the higher speed supernatant of the rat heart homogenate and the regional distribution of L-threo-DOPS decarboxylase activity were examined. Decarboxylation was demonstrated to occur specifically with L-isomer but not with D-isomer. Addition of pyrogallol was necessary for maximal recovery of norepinephrine. The optimal condition for decarboxylation of L-threo-DOPS by the rat heart enzyme was similar to conditions required with the enzymes from brain and kidney. Under the optimal conditions, Km and Vmax for L-threo-DOPS were 2.1 mM and 6.4 nmoles/mg protein/15 min, respectively. Decarboxylation of L-threo-DOPS was markedly inhibited by D-threo-DOPS and D-DOPA. The L-aromatic amino acid decarboxylase activity was highest in the right auricle followed by the atrial body, the left auricle, the right ventricle and the left ventricle.

Animals↗
PubMed1987

Effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS), an immediate precursor of norepinephrine, on the cerebral blood flow in rats.

L-threo-3,4-Dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) precursor, 3 mg/kg, i.v., increased the cerebral blood flow (CBF) in both the striatum and hippocampus as well as the mean arterial blood pressure (MABP) in urethane-anesthetized rats, as NE infusion did. The L-DOPS induced increase in CBF was inhibited by benserazide (3 mg/kg/hour), a peripheral aromatic L-amino acid decarboxylase inhibitor, and propranolol (3 mg/kg, i.p.), a beta-adrenoceptor blocker as well. These results suggest that the effects of L-DOPS may be attributed to the action of NE formed from L-DOPS, and the action may be mediated by stimulation of beta-adrenoceptor.

Animals↗
PubMed1988

Inhibitory effects of L-threo-DOPS, an L-noradrenaline precursor, on locus coeruleus-originating neurons in the caudate nucleus.

Electrophysiological studies using reserpine-treated cats were carried out to elucidate the effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the noradrenergic pathway from the locus coeruleus (LC) to the caudate nucleus (CN) neurons, which were activated by iontophoretically applied bromocriptine, a dopamine D-2 receptor agonist. In the CN neurons, glutamate-induced firing was inhibited by iontophoretic application of noradrenaline, but not by repetitive stimulation of the LC or iontophoretically applied L-threo-DOPS. After intraventricular administration of L-threo-DOPS, however, LC stimulation inhibited the glutamate-induced firing. These results suggest that L-noradrenaline that was produced from the conversion of L-threo-DOPS inhibited the CN neurons which possess dopamine D-2 receptors.

Animals↗
PubMed1990

Diuretic effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) in anesthetized rats.

A synthetic amino acid, L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), can be converted to (-)-norepinephrine (NE) by aromatic L-amino acid decarboxylase (AADC) in various mammalian tissues. Recent studies have indicated the pressor and diuretic effects of L-threo-DOPS. In this study, we examined the effects of L-threo-DOPS on renal hemodynamics and function in anesthetized rats, and evaluated possible mechanisms of the diuresis. Intravenous infusion of L-threo-DOPS at 120 micrograms/kg/min exerted a significant increase in mean arterial pressure (MAP). There was a slight but nonsignificant decrease in renal blood flow (RBF). Although the glomerular filtration rate (GFR) remained at a constant level, urine flow (UF) and urinary sodium excretion (UNaV) increased significantly during the drug infusion. Pretreatment with AADC inhibitor, benserazide, completely blocked both the pressor and diuretic effects of L-threo-DOPS. When the renal perfusion pressure was protected from the pressor effect of the drug by using a Blalock clamp, the drug-induced diuresis was abolished. The diuretic effect of L-threo-DOPS was markedly attenuated by the administration of phentolamine. There was a positive correlation between plasma NE concentration and UF during the infusion of L-threo-DOPS. Intrarenal arterial infusion of L-threo-DOPS at 20 micrograms/kg/min was without effect on renal function. These results indicate that diuresis and natriuresis induced by L-threo-DOPS are dependent on the pressor effect of NE via peripheral alpha-adrenoceptor activation.

Anesthesia↗
PubMed1976

[The histaminergic mechanisms in the regulation of prolactin secretion in urethan-anesthetized rats (author's transl)].

In an attempt to detect the existence of histaminergic mechanisms in the regulation of prolactin secretion in rats, the effects of histidine and histamine-receptor antagonists (chlorpheniramine and metiamide) on plasma prolactin levels in urethan-anesthetized rats were investigated in relation to other aminergic mechanisms. Chlorpheniramine was used as an H1-receptor antagonist and metiamide as an H2-receptor antagonist. Wistar male rats were used under urethan anesthesia and blood was obtained by cardiac puncture. Rat plasma prolactin was measured by radioimmunoassay. As already reported, L-DOPA and diethyldithiocarbamate markedly decreased plasma prolactin levels in rats. Dihydroxyphenylserine increased prolactin levels. Brocresine phosphate, a histidine decarboxylase inhibitor, markedly stimulated prolactin secretion in urethan-anesthetized rats. This stimulation was not blocked by pretreatment with histidine or L-DOPA. Histidine alone did not affect plasma levels of prolactin or methyldopamine-induced increase in plasma prolactin levels. On the other hand, histidine significantly stimulated prolactin secretion in chlorpheniramine-treated rats. In contrast, histidine depressed plasma prolactin levels in metiamide-treated rats. These findings indicate that a dopaminergic component is inhibitory and a noradrenergic one is stimulatory in prolactin secretion in rats and further that there exist the histaminergic mechanisms, relatively independent from other aminergic mechanisms, which might also play an important role in the regulation of prolactin secretion in rats. Furthermore, it is suggested that H1-receptor is stimulatory and H2-receptor is inhibitory in prolactin secretion in rats.

Animals↗
PubMed1981

Further evidence of the dual role of noradrenaline in regulation of thyrotrophin secretion in male rats.

The dual role previously suggested for noradrenergic neurons in TRH-TSH regulation was studied in male rats. Alpha-Methyl-p-tyrosine (alpha MPT) significantly decreased brain noradrenaline (NA) and dopamine (DA) levels 0.5-6 h after the injection. Maximum inhibition of TSH cold-response occurred at 4 h. One h after administration of L-dopa the brain DA (but not NA) level was considerably elevated. TSH cold-response was not significantly changed. The effects of alpha MPT and Ca-fusarate on the cold-induced TSH secretion were antagonized by neither dihydroxyphenylserine (DOPS; this drug restores NA stores) nor by L-dopa (which restores DA levels). DOPS even potentiated the depressive effect of alpha MPT and Ca-fusarate. When given into the third ventricle, NA did not modify basal TSH levels but decreased the cold-induced TSH secretion. When infused directly into the median eminence of the medial basal hypothalamus, NA reduced both basal and cold-induced TSH secretion. Pinealectomy decreased the TSH cold-response but NA seemed to retain its ability to inhibit TSH secretion. These results demonstrate that besides the possible stimulatory action on TSH secretion, noradrenergic neurons also have an inhibitory effect outside the blood-brain barrier, possibly in the median eminence.

Animals↗
PubMed1999

L-DOPS-Accelerated recovery of locomotor function in rats subjected to sensorimotor cortex ablation injury: pharmacobehavioral studies.

Central norepinephrine (NE) has been shown to play a beneficial role in amphetamine-facilitated recovery of behavior. To give insight into understanding the mechanism, the present studies were conducted to examine (a) the effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) combined with benserazide (BSZ; a peripheral aromatic amino acid decarboxylase inhibitor) and L-3,4-dihydroxyphenylalanine (L-DOPA), precursors of NE and dopamine (DA), respectively, on the recovery from beam-walking performance deficits in rats subjected to unilateral sensorimotor cortex ablation injury, and (b) the relationships between the behavioral recovery and the frequency of postoperative training and the size of ablation injury. It was found that the combined treatments with L-DOPS and BSZ promoted the recovery of locomotor function as early as 24 hours after injury. L-DOPA alone, however, did not facilitate behavioral recovery. The results of assay for the tissue levels of NE and its major metabolite (3-methoxy-4-hydoxyphenylethylene glycol; MHPG) in the brain using high-pressure liquid chromotography showed MHPG, but not NE, significantly increased in the cerebellum and the hippocampus. The behavioral recovery was also significantly correlated with the frequency of training subsequent to injury, but inversely with the size of cortex ablation. These results suggest that NE is likely to modulate functional recovery in this rodent model.

Animals↗
PubMed1984

Improvement in freezing phenomenon of Parkinson's disease after DL-threo-3, 4-dihydroxyphenylserine.

A 77-year-old man with Parkinson's disease of long standing, under treatment with L-DOPA and benserazide, was administered DL-threo-3, 4-dihydroxyphenylserine (DL-threo-DOPS), a precursor of norepinephrine, for 10 days. With this administration the patient's freezing phenomenon was remarkably improved, and his dysarthria also showed improvement. When DL-threo-DOPS was suspended, the frozen gait returned on the third day to almost the former level, even though he continued to receive L-DOPA and benserazide. After administration of DL-threo-DOPS, the CSF level of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of norepinephrine, was 127.5% of the pretreatment level. These observations suggest that DL-threo-DOPS can pass through the blood-brain barrier and change to norepinephrine, and that DL-threo-DOPS may be beneficial in the treatment of the freezing phenomenon of Parkinson's disease.

Aged↗
PubMed1984

Anti-parkinsonian drugs today.

The drug treatment of Parkinson's disease has progressed through 3 main stages: firstly, the use of anticholinergic drugs and amantadine; then the introduction of levodopa and its association with peripheral decarboxylase inhibitors; and finally the use of direct acting dopamine agonist drugs. Levodopa, however, remains the most effective single drug in Parkinson's disease. Unfortunately, the side effects associated with long term levodopa treatment today constitute an important cause of functional disability. 'Positive' side effects such as involuntary movements and psychiatric disorder remain difficult to manage without causing an increase in Parkinsonian immobility; conversely, management of the 'negative' phenomenon of the 'off' period is limited by these same side effects. This has generated renewed interest in the highly complex pharmacokinetic and pharmacodynamic properties of levodopa, with the aim of reducing fluctuations in plasma levodopa (and hence brain dopamine) concentrations by sustained release oral or continuous parenteral administration of the drug.

Amantadine↗
PubMed1989

L-threo-3,4-dihydroxyphenylserine treatment for gait apraxia in parkinsonian patients.

L-threo-3,4-dihydroxyphenylserine (L-DOPS) was administered to six parkinsonian patients for the treatment of gait related akinesia which was refractile to L-DOPA treatment. One responded with marked improvement and one with only mild improvement. Although number of patients who respond markedly to this noradrenaline precursor, L-DOPS, is limited, L-DOPS was felt to be the most effective treatment modality for L-DOPA refractile gait related akinesia and L-DOPA related orthostatic hypotension.

Aged↗
PubMed1995

The role of L-threo DOPS in the control of Na-K ATPase activity of the marginal cells in the stria vascularis of reserpinized guinea pigs.

It is believed that the function of the stria vascularis in the cochlea is to produce endolymph. The mechanisms that maintain or control the function of the stria vascularis, however, remain unclear. In a previous study, we investigated the ultracytochemical effects of one-shot reserpine administration on the Na-K ATPase activity of the stria vascularis in guinea pigs. Na-K ATPase activity was shown to be completely inhibited 3-20 days after reserpinization, whereas in the present study at 20 days after reserpinization and following L-threo DOPS treatment, Na-K ATPase activity was detectable. As reserpine is an adrenergic neuron blocker, and L-threo DOPS is the precursor of noradrenaline, it seems that noradrenaline converted from L-threo DOPS was able to restore the Na-K ATPase activity in the reserpinized animals. These results suggest that catecholamines may play an essential role in the maintenance or control of the Na-K ATPase activity, and that the stria vascularis may be one of the target organs of catecholamines.

4-Nitrophenylphosphatase↗