Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lisuride”

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 37 records · Page 2Linked to original sources

[Effects in animal models of depression of lisuride alone and upon coadministration with antidepressants].

Effects of lisuride, a central dopamine and serotonin agonist of the ergot type, in animal models of depression were investigated in comparison with those of desipramine, mianserin and rolipram. Lisuride, like desipramine and mianserin, inhibited reserpine-induced hypothermia in mice (0.5-5.0 mg/kg, i.p.) and suppressed muricide in olfactory bulbectomized rats (ED50 = 0.16 mg/kg, i.p.) in a dose-dependent manner. The anti-muricidal effect was slightly enhanced by the repeated administration of 0.25 mg/kg lisuride. Lisuride (0.05-0.25 mg/kg, i.p.), like desipramine, dose-dependently reduced the duration of immobility in rats forced to swim, and this effect was antagonized by haloperidol. The reduction of immobility time was enhanced by the repeated administration of lisuride; at the same time, the ambulation in rats increased. Furthermore, the immobility-reducing effects of desipramine and rolipram were markedly enhanced by the co-administration of a low dose of lisuride (0.025 mg/kg, i.p.), which by itself had no effect on the immobility time. These results indicate that lisuride may be useful for the treatment of depression and indicate that a low dose of lisuride may enhance the clinical effectiveness of antidepressants such as desipramine.

Agonistic Behavior↗

[Treatment of hyperprolactinemia and acromegaly with lisuride].

17 hyperprolactinemic and 2 acromegalic patients, aged 19-73, and 47 and 59 years, respectively, were treated with Lisuride (dopergin). 12 of the hyperprolactinemic patients were treated with Lisuride because they could not tolerate the side effects of bromocriptine (Group A), and the other 5 because large doses of bromocriptine failed to reduce their plasma prolactin to normal (Group B). The 2 acromegalic men, were treated with Lisuride because of persistently high levels of growth hormone after hypophysectomy and irradiation of the sella turcica, and because of intolerance to bromocriptine. Lisuride reduced prolactin to normal in 11 of the 12 in Group A (from 217 +/- 175 to 27 +/- 10 micrograms/l, p less than 0.01) and reduced it in the last patient from 3900 to 270 micrograms/l. The prolactin-lowering effect of Lisuride was unsatisfactory in Group B since like bromocriptine, it failed to reduce prolactin levels. One of the acromegalics improved both clinically and biochemically and growth hormone levels were reduced from 56 to 18 ng/ml, while the other did not respond to Lisuride. Its main side effects were somnolence, nausea, and increased appetite (4 patients). These effects lasted only a few weeks. One patient stopped Lisuride because of severe constipation, which had been caused by bromocriptine as well. Lisuride is an effective drug in hyperprolactinemia, especially in those with severe side effects after other dopaminergic drugs. It is effective in some cases of acromegaly, but has little to offer to those resistant to bromocriptine.

Acromegaly↗

Discriminative stimulus properties of lisuride revisited: involvement of dopamine D2 receptors.

Although the discriminative stimulus effects of the clinically useful ergot derivative lisuride have previously been related to dopamine (DA) neuronal systems, the involvement of DA D1 and D2 receptor subtypes in the lisuride cue has been characterized for the first time in the present experiment. In rats trained to discriminate lisuride (0.04 mg/kg) from saline, appropriate doses of the putative D2 agonist LY 171555 (0.008-0.063 mg/kg) substituted completely whereas the D1 agonist SKF 38393 (2.0-16.0 mg/kg) evoked primarily saline-lever responding. When given in combination with lisuride (0.04 mg/kg), the D2 antagonist (-)-sulpiride (5-30 mg/kg), but not the D1 antagonist SCH 23390 (0.125-0.5 mg/kg), blocked the lisuride cue. Combination tests also suggested that bromuride and pirenperone have DA antagonist properties. Although the specificity of these agents is not fully known, these results support the conclusion that D2 but not D1 receptors play an important role in the stimulus effects of lisuride. Although a role for serotonin in the similar stimulus properties of lisuride and SCH 23390 cannot be ruled out, partial substitution of SCH 23390 (0.0625-0.35 mg/kg; administered alone) for lisuride complements previous observations which suggest that the two DA subtypes may be functionally linked in vivo.

Animals↗

The interaction of lisuride, an ergot derivative, with serotonergic and dopaminergic receptors in rabbit brain.

The interaction of lisuride (Lysenyl, Spofa), an ergot derivative, with serotonergic and dopaminergic receptors and with adenylate cyclase was studied in homogenates of rabbit brain. In frontal cortex, lisuride interacts with serotonin receptors as shown by its ability to compete with [3H]serotonin, [3H]spiroperidol and [3H]lysergic acid diethylamide for their receptor binding sites, with respective IC50 values of 14, 1.0 and 3.7 nM. The IC50 for displacement of [3H]spiroperidol by lisuride in frontal cortex was increased by the GTP analog, 5'-guanylylimidodiphosphate, indicating an agonist-like interaction. Lisuride is extraordinarily potent in stimulating serotonin-sensitive adenylate cyclase in this brain region, with maximal stimulations occurring at 0.1 nM lisuride. In caudate nucleus, lisuride interacted with both serotonergic and dopaminergic receptor sites as labeled by [3H]serotonin, [3H]lysergic acid diethylamide and [3H]2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene, with IC50 values ranging from 2.0 to 7 nM. Lisuride did not stimulate adenylate cyclase in caudate nucleus. In summary, lisuride is a very potent stimulator of serotonin-sensitive adenylate cyclase in rabbit frontal cortex and can interact with serotonin and dopamine receptor binding sites in rabbit cortex and caudate nucleus.

Adenylyl Cyclases↗

Dual activation by lisuride of central serotonin 5-HT(1A) and dopamine D(2) receptor sites: drug discrimination and receptor binding studies.

To investigate central serotonergic (5-HT) and dopaminergic (DA) actions of lisuride, the discriminative properties of lisuride (0.05mg/kg, i.p.) in rats were investigated, in addition to the radioligand binding of the compound to 5-HT and DA receptor subtypes. Lisuride was found to possess high affinities for 5-HT(1A) receptor sites (Ki=0.5nM) and D(2) receptor sites (Ki=2.0nM). The autoradiographic binding pattern of 4nM [(3)H]lisuride in rat brain showed high densities of sites displaceable by the 5-HT(1A) agonist 8-OH-DPAT in hippocampus, lateral septal nucleus and amygdala, as well as those displaceable by the D(2) antagonist sulpiride in striatum, nucleus accumbens and olfactory tubercle. In drug discrimination tests, the mixed, D(1)/D(2) agonist apomorphine, the partial D(2) receptor agonists (-)-3-PPP and terguride and the 5-HT(1A) agonist 8-OH-DPAT substituted for lisuride. The D(1) agonist SKF38393, the D(1) antagonist SCH23390, the D(2) antagonist sulpiride, the 5HT(1B) agonist m-CPP and the 5-HT(2) agonist DOI were not generalized to the lisuride cue. In antagonism tests, the D(2) antagonist haloperidol and the 5-HT antagonist methysergide both induced partial but significant antagonism to the lisuride cue, but the D(1) antagonist SCH23390 did not. These results indicate that discriminative stimulus properties of lisuride are mediated by the dual activation of 5-HT(1A) and D(2) receptor sites in brain.

Journal Article↗

Influence of lisuride on morphine withdrawal signs in the rat: a dopamine-mimetic effect.

The influence of lisuride on naloxone-induced withdrawal signs (wet shakes, escape attempts) was studied in morphine-dependent rats. Lisuride, injected IP at doses of 12.5 and 25 micrograms/kg, inhibited wet shakes while not significantly altering escape attempts induced by naloxone (4 mg/kg IP). At higher doses (50 and 100 micrograms/kg IP), lisuride's inhibitory effect on wet shakes persisted while escape attempts were actually potentiated with respect to control withdrawal rats. Increases in aggressive behavior were seen at all doses, and were dose-related. Haloperidol (0.3 mg/kg IP), administered 40 min before lisuride, did not modify the antagonistic effect on wet shakes, unlike sulpiride (40 mg/kg IP 30 min before lisuride), but at the same time blocked the increase in escape attempts and aggressiveness induced by lisuride. We suggest that lisuride modulates withdrawal signs by stimulation of dopamine receptors in the CNS. The effect of the dopamine mimetic N-n-propylnorapomorphine (NPA) on the same variables is reported as well as the influence of haloperidol on NPA, and a comparison between the effects of the two drugs is made.

Aggression↗

Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors.

Evidence from studies with phenylisopropylamine hallucinogens indicates that the 5HT2A receptor is the likely target for the initiation of events leading to hallucinogenic activity associated with LSD and related drugs. Recently, lisuride (a purported non-hallucinogenic congener of LSD) was reported to be a potent antagonist at the 5HT2C receptor and an agonist at the 5HT2A receptor. LSD exhibited agonist activity at both receptors. These data were interpreted as indicating that the 5HT2C receptor might be the initiating site of action for hallucinogens. To test this hypothesis, recombinant cells expressing 5HT2A and 5HT2C receptors were used to determine the actions of LSD and lisuride. LSD and lisuride were potent partial agonists at 5HT2A receptors with EC50 values of 7.2 nM and 17 nM, respectively. Also, LSD and lisuride were partial agonists at 5HT2C receptors with EC50 values of 27 nM and 94 nM, respectively. We conclude that lisuride and LSD have similar actions at 5HT2A and 5HT2C receptors in recombinant cells. As agonist activity at brain 5HT2A receptors has been associated with hallucinogenic activity, these results indicate that lisuride may possess hallucinogenic activity, although the psychopharmacological effects of lisuride appear to be different from the hallucinogenic effects of LSD.

3T3 Cells↗

Tolerance to hypoactivity and sensitization to hyperactivity after chronic treatment with a presynaptic dose of lisuride in rats.

We studied the adaptive changes of the locomotor effects of lisuride, a selective agonist for dopamine (DA) D2 receptors, and the functional state of D1 and D2 receptors after repeated administration of lisuride at a dose supposed to act preferentially on DA autoreceptors. Rats were treated daily with saline or lisuride, at a dose that causes a significant reduction in locomotor activity when given to naive rats (25 micrograms/kg i.p.), for 33 days and the effect of different challenging doses of the drug on locomotor activity was measured at different times during and after the treatment. The functional state of D1 and D2 DA receptors was evaluated by measuring SKF 82526-stimulated and LY 171555-inhibited adenylate cyclase (AC) activity in the caudatus/putamen, nucleus accumbens and substantia nigra and naive and chronically treated rats. There was a progressive decline in the ability of lisuride to decrease locomotor activity in rats given daily injections of lisuride, and there was a marked reduction in the threshold dose of lisuride for causing hypermotility. The functional state of DA receptors, positively or negatively linked to AC activity, was not modified by the treatment. The most suitable explanation of the reported adaptive behavioral changes is a down-regulation of DA autoreceptors after chronic treatment with presynaptic doses of lisuride.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

The effect of lisuride hydrogen maleate on anterior pituitary hormones, oestradiol and cortisol in normal and hyperprolactinaemic women.

The effects of single oral doses of 0.1 mg lisuride hydrogen maleate (lisuride), a semisynthetic ergot derivative given at 09.00 h, on the serum levels of prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), thyroid-stimulating hormone (TSH), oestradiol and cortisol were studied in six normally cycling women and six patients with hyperprolactinaemic amenorrhoea. The same subjects received placebo and the results were compared with those of lisuride. Within 1 h after oral administration of lisuride, PRL levels decreased significantly (P less than 0.05) and reached the lowest level at 4 h after ingestion and stayed low until 8 h in both normal women and hyperprolactinaemic patients. LH levels slightly but not significantly decreased after lisuride administration in hyperprolactinaemic patients. Serum cortisol levels increased at 13.00 h, probably due to the effect of meal. No significant differences between the lisuride group and placebo group were observed in GH, TSH, FSH and oestradiol levels. These results suggest that lisuride acts as a long-acting prolactin suppressor and that it has little effects on the secretion of other pituitary hormones. Therefore, this drug could be useful for treatment of hyperprolactinaemic patients.

Adult↗

Evidence for a direct dopaminergic effect of lisuride.

The discriminative stimulus properties of the clinically important ergot derivative lisuride hydrogen maleate were studied by training 2 groups of rats to discriminate 0.04 mg/kg lisuride from saline and 0.16 mg/kg apomorphine from saline. Dose-response and substitution tests between these groups showed that lisuride and apomorphine are discriminated similarly by both groups and that lisuride is 5 to 9 times more potent. The dopaminergic agonists d-amphetamine, quipazine, bromocriptine, cocaine and cathinone did not substitute for lisuride. In antagonism studies, only the dopamine receptor blocker haloperidol attenuated the lisuride cue; the serotonin receptor blockers pirenperone and BC-105 were ineffective. These data indicate that the primary central action mediating the discriminative stimulus effects of lisuride was direct activation of dopamine receptors.

Animals↗

Lisuride reduces intravenous cocaine self-administration in rats.

The maintenance of intravenous (i.v.) cocaine self-administration appears to depend upon activation of dopamine terminals within mesocorticolimbic areas. Since the nonaddictive ergot derivative lisuride is a direct dopamine receptor agonist, the present study was designed to investigate whether administration of lisuride to rats trained to lever-press for IV self-administration of cocaine could affect the intake of cocaine. IP administration of several doses of lisuride reduced, in a dose-dependent manner, cocaine self-administration. In a control experiment, lisuride did not increase the psychomotor-activating properties of cocaine as measured by locomotor activity, suggesting that lisuride did not simply potentiate the activating effects of cocaine. The present results show that lisuride reduced IV cocaine self-administration in rats; the possibility of a new therapeutic approach to the treatment of cocaine abuse in humans using lisuride may therefore deserve clinical attention.

Animals↗

The dopamine receptor agonist lisuride attenuates iron-mediated dopaminergic neurodegeneration.

Many dopamine agonists used in the treatment of Parkinson's disease are suggested to be potentially neuroprotective. On the basis of its structure, the dopamine agonist lisuride may share this characteristic. In the current study discrete asymptomatic lesions were produced by the injection of iron-laden neuromelanin into the rat substantia nigra and the animals treated with lisuride to determine the protective potential of this substance. Two treatment regimes were utilised. In the neuroprotective protocol, animals were treated with 0.1 mg.kg(-1) lisuride twice daily 3 days prior to, and 7 days following, the iron lesion. In the neurorescue protocol, the animals received 0.1 mg.kg(-1) lisuride twice daily for 1 week beginning on the fourth day post surgery. Eight weeks post surgery, tyrosine hydroxylase-positive neurons surrounding the injection site (33% of total nigral volume) were counted. Dopamine neuron number in iron-lesioned animals was reduced to 50% of that in vehicle-injected animals. The absence of motoric disturbances or a striatal dopamine deficit in these animals suggests a subclinical dopaminergic lesion. Dopamine neuron number in the quantified area in sham-injected animals receiving lisuride or iron-lesioned animals receiving lisuride in both the neuroprotection and neurorescue groups were not significantly reduced. These results suggest that lisuride can protect neurons against iron-induced cell death and might thus be neuroprotective in Parkinson's disease.

Aerobiosis↗

Lisuride in the treatment of parkinsonism.

Lisuride is a new effective antiparkinson agent that is useful in the management of patients in an advanced stage of parkinsonism where levodopa therapy is no longer sufficient and/or limited by 'wearing off' reactions. Patients with these problems usually respond favorably to 1.5-4.5 mg of lisuride daily provided the daily dose is built up gradually over a period of 4-8 weeks. All the clinical features of parkinsonism may be improved and the daily dose of levodopa may be reduced by 30-40%. In some instances it may be possible to give lisuride as a replacement for levodopa. Less established, however, is the potential role of lisuride in treating patients in the early stages of parkinsonism and the long-term effects of lisuride. And, as with other ergots, caution should be exercised in using lisuride if patients have a history of hypotension, hepatic dysfunction, cardiac arrhythmias, and dementia. Finally, lisuride, unlike other drugs, is highly water soluble with a nearly immediate outset of antiparkinsonian action when given intravenously and may therefore be of considerable value in the emergency treatment of severe parkinsonism.

Administration, Oral↗

Lisuride, a dopamine agonist, inhibits DNA synthesis in the pituitary gland.

We investigated the effects of lisuride, a potent dopaminergic agent, administered in vivo on the incorporation of 3H-thymidine into DNA and 3H-leucine into prolactin and its subsequent release by the rat anterior pituitary gland in vitro. The results demonstrated that daily injection of 100 micrograms of lisuride for 7 days significantly (p less than 0.05) diminished (about 35%) the incorporation of 3H-thymidine into DNA and reduced the stimulation of DNA synthesis produced by estrogens. The incorporation of 3H-leucine into prolactin was markedly inhibited by the administration of lisuride, and also significantly (p less than 0.05) reduced the stimulation of prolactin secretion produced by estrogens. In pituitary glands enlarged by the chronic administration of estrogens, lisuride treatment significantly (p less than 0.05) reduced the weight (26%), the content of DNA (35%) and the incorporation of 3H-thymidine (40%). The inhibitory effect of lisuride on DNA synthesis was present as early as 20 h after a single injection of the drug (about 27%). The same treatment with lisuride significantly (p less than 0.05) reduced the incorporation of 3H-leucine into prolactin. The results of these experiments are compatible with the concept of a relationship between prolactin release and DNA synthesis in the pituitary gland. They also suggest that lisuride, as with bromocriptine, may exert its antiproliferative effects on prolactin-secreting adenomas by decreasing their synthesis of DNA.

Animals↗

[11C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease: Influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors.

We studied cerebral dopamine D2-receptor binding using [11C]raclopride and PET in 18 previously untreated patients with Parkinson's disease (PD) and 14 healthy volunteer subjects. Sixteen patients were scanned before and after 3 to 4 months of stable oral therapy with either L-dopa (300 mg/d) (n = 7) or lisuride (0.8 to 1.2 mg/d) (n = 9). Two additional patients were investigated before and after a continuous IV infusion of L-dopa. In addition, we studied the effect of acute IV L-dopa and lisuride administration on [11C]raclopride binding in a healthy rhesus monkey. At baseline, PD patients showed higher uptake values in the putamen than did healthy subjects (p < 0.0001). Oral lisuride treatment lowered [11C]raclopride uptake in the putamen (-19%) and in the caudate nucleus (-15%) compared with baseline, but the difference did not reach significance upon Bonferroni correction for multiple comparisons. However, putamen tracer uptake returned to baseline in two patients when we repeated [11C]raclopride scans 4 days after lisuride withdrawal. Oral L-dopa treatment did not induce changes in the putamen or caudate nucleus indices. Acute lisuride (25 micrograms) administration in a healthy monkey reduced striatal uptake values, but acute injection of L-dopa (300 mg) did not. The results suggest that lisuride blocks [11C]raclopride binding at dopamine D2-receptor sites and demonstrate that 3 to 4 months' oral therapy with L-dopa or lisuride does not change striatal dopamine D2-receptor density in PD patients.

Adult↗

Lisuride treatment in Parkinson's disease: clinical and pharmacokinetic studies.

Our study of 28 patients has shown lisuride to share a comparable profile of antiparkinsonian effects and adverse reactions to that found with bromocriptine. The similarity in clinical response to lisuride and bromocriptine in the same group of patients contrasts with the pharmacological differences that have been established between them in animal studies. There were considerable individual differences in the patients' preference of bromocriptine or lisuride. The daily intake requirements of each drug for optimal benefit also varied widely from one patient to another. The preliminary results of pharmacokinetic studies with lisuride suggest several explanations for the differences in daily dosage requirements. Although the mean optimal daily dose of lisuride was 4.5 mg, some patients required up to 10 mg. Eleven of the patients have continued on lisuride for more than 1 year. Our clinical impression is that problems with chronic levodopa therapy, such as dyskinesia and fluctuations in efficacy, are reduced in some patients taking either lisuride or bromocriptine.

Bromocriptine↗

[Brain SPECT with 123I-lisuride in patients with Parkinson's disease and controls].

The goal was to visualize cerebral dopamine-D2 receptors in 6 patients with Parkinson's disease and in 3 healthy controls using iodine-123-Lisuride-SPECT. In addition, we performed receptor-replacement studies using 123I-Lisuride and cold Lisuride as competitive ligands. The highest uptake of 123I-Lisuride was observed in the striatum, a region with known high dopamine receptor density. In two patients premedication with cold Lisuride displaced 123I-Lisuride from the dopamine receptor. 123I-Lisuride is valuable as a radiotracer in cerebral dopamine-D2 receptor scintigraphy. Whether or not it is possible to determine dynamic changes of dopamine receptor density or function by receptor replacement studies needs further evaluation in larger patient populations.

Adult↗

A study on the effect and tolerance of lisuride on Parkinson's disease.

Seventeen idiopathic parkinsonian patients ranging between 47 and 75 years of age were included in this study to investigate the effect and tolerance of lisuride on PD. The duration of this simple clinical study, which had no control group was 12 weeks. There was 50% relief in disability scores and ADL in 13 patients in the first group in the combined therapy for 12 weeks with lisuride added to L-DOPA plus benserazide (p < 0.01). Optimal lisuride doses added to L-DOPA plus benserazide varied between 0.1 and 0.8 mg (mean 0.5 +/- 0.2 mg). With the addition of lisuride to treatment, the L-DOPA plus benserazide dose was reduced in 6 of 13 by 38%. Monotherapy with lisuride resulted in 56% to 57% improvement in disability scores and 47% in relief in ADL. Dry mouth, nausea, weakness, postural hypotension, and headache were the most frequently encountered side effects of lisuride. These adverse effects disappeared in 3 or 4 days, depending on a slight decrease and following increase in the dose of lisuride and/or the development of tolerance. Not only will such a combined therapy contribute to the reduction of the end-of-dose inadequacies, on-off phenomena, wearing off, peak-dose dyskinesias, and similar motor fluctuations, it may also play a prophylactic role in their prevention or delay.

Age of Onset↗