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At least 19 recordsLinked to original sources
PubMed1981

Radioimmunoassay of plasma lisuride in man following intravenous and oral administration of lisuride hydrogen maleate: effect on plasma prolactin level.

The development of a sensitive radioimmunoassay for the determination of lisuride in plasma is described. The antiserum against lisuride-4-hemisuccinate-BSA was raised in rabbits. Using this method the plasma levels of lisuride were monitored following one intravenous (25 microgram) and two oral (100 microgram and 300 microgram) doses of lisuride hydrogen maleate in three female and three male volunteers (intra-individual comparison). The plasma prolactin was also determined by radioimmunoassay. Following i. v. injection, the concentration of lisuride declined in three phases, with half-lives of 5 min, 25 min and 2 h. The total plasma clearance of 800 +/- 250 ml X min-1 was in the range of "plasma flow" through the liver. In agreement with the high rate of biotransformation, the bioavailability of lisuride administered orally was 10% +/- 7% of the 100-microgram dose, and 22% +/- 7% of the 300-microgram dose. The plasma prolactin was lowered to 3%-18% of its pretreatment value depending on the route of administration and the dose. The reduction appeared to be short-lived and to be directly dependent on the plasma concentration of lisuride. Following intravenous injection, the prolactin level declined after a so far unexplained lag-time of 0.5 h.

Administration, Oral↗
PubMed1981

Lisuride in Parkinson disease: efficacy of lisuride compared to levodopa.

Lisuride hydrogen maleate, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was tested in 10 patients with moderate to marked Parkinson disease whose response to levodopa had diminished. In the group of 10 patients, there was a significant reduction (p less than or equal to 0.05) in bradykinesia, gait disorder, and total Parkinson disease disability score when levodopa was replaced with lisuride. The mean dose of lisuride was 3.6 mg per day. Among the 10 patients, 5 were better on lisuride than on levodopa, and 4 continue on lisuride 1 year later. A decline in efficacy was noted in all four after a mean of 45 months. Adverse effects necessitating discontinuing the drug were mental changes in three patients and nausea in one patient. Lisuride, when used alone, has definite antiparkinsonian activity and is a promising new drug.

Aged↗
PubMed1981

Activity of a non-hallucinogenic ergoline derivative, lisuride, in an animal behavior model for hallucinogens.

The behavioral effects of IP administration of lisuride, a non-hallucinogenic iso-lysergic acid amide analog structurally related to d-lysergic acid diethylamide (LSD), were examined in 15 cats. Ten animals were given saline or 6.25, 12.5, 25, 50, or 100 micrograms/kg of lisuride and observed for 1 h by a rater blind to dose. There was a statistically significant effect of lisuride dose on the frequency of occurrence of the behaviors limb flicking, grooming, and abortive grooming. A time-course study with five cats at the most effective lisuride dose, 50 micrograms/kg, revealed that the frequencies of occurrence of these behaviors reached a maximum during the first 2 h post dose, and were comparable to frequencies after saline by 6 h post dose. An acute tolerance study with four cats scored for 90 min post dose revealed no significant tolerance to a 50 micrograms/kg lisuride test dose administered 6, 24, or 72 h after an initial 50 micrograms/kg dose. Acute cross tolerance studies with four cats scored for 90 min after an initial dose of 50 micrograms/kg of LSD or of lisuride, followed 24 h later by 50 micrograms/kg of lisuride or LSD, revealed no significant cross tolerance. The potency of lisuride relative to LSD was evaluated in six cats that were scored for 60 min following 25 and 50 micrograms/kg of LSD and of lisuride. On a molar basis, scores after lisuride were 51% and 67% those after LSD for limb flicking and grooming. These results indicate that lisuride, a non-hallucinogenic iso-lysergic acid derivative, is a false positive in the animal behavior model for hallucinogens.

Animals↗
PubMed1977

Effect of lisuride and other ergot derivatives on monoaminergic mechanisms in rat brain.

The effects of the ergot derivative lisuride hydrogen maleate on synthesis, turnover and receptor activity of monoamines were compared with those of LSD, methysergide, yohimbine and methiothepin. In the dopamine (DA) rich areas, c. striatum and mesolimbic forebrain, lisuride, (30-100 mug/kg) decreased the rate of dopa formation after inhibition of the aromatic amino acid decarboxylase with NSD 1015, 100 mg/kp i.p. After axotomy of the ascending monoaminergic fibers, lisuride (0.5 mg/kg) antagonized the accumulation of dopa in c. striatum and mesolimbic forebrain even on the lesioned side; haloperidol effectively counteracted this lisuride-induced decrease in dopa formation. In the predominantly noradrenaline (NA)-innervated neocortex, lisuride in doses of 0.3 and 1.0 mg/kg increased dopa accumulation. Methysergide, yohimbine and methiothepin also stimulated tyrosine hydroxylation. After inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine methylester HCl, lisuride decelerated DA disappearance and accelerated NA disappearance. 3-Methoxytryramine (3-MY) accumulating after inhibition of monoamine axidase with pargyline HCl (100 mg/kg) was used as an indicator of DA release. Lisuride and LSD, 50 mug/kg administered twice, reduced 3-MT formation while methysergide, 50 mg/kp i.p. had no effect on 3-MT accumulation. All compounds except methiothepin reduced 5-hydroxytryptophan (5-HTP) accumulation in whole brain after NSD 1015. In addition, lisuride caused an increase in 5-hydroxytryptamine (5-HT) and a decrease in 5-hydroxyindole acetic acid concentration. In spinal reserpinized rats, lisuride was indistinguishable from LSD in inducing extension and athetoid movements of the hind legs. The data support the view that lisuride stimulates pre- and postsynaptic DA and 5-HT receptors and suggest that lisuride blocks NA receptors in the central nervous system.

Animals↗
PubMed1991

[Anxiolytic effects of lisuride and its agonistic action to central 5-HT1A receptors].

Effects of lisuride, a derivative of ergot alkaloid, on central 5-HT1A receptors were investigated biochemically, behaviorally and electroencephalographically (EEG) in rats and rabbits. Effects of lisuride in water-lick conflict tests were also investigated in rats. Lisuride was found to strongly inhibit the bindings of [3H]8-OH-DPAT to 5-HT1A receptors in the raphe nucleus, hippocampus, cortex, amygdala and hypothalamus of rat brain. Inhibitory effects of lisuride on bindings of [3H]8-OH-DPAT in the hippocampus was almost the same as that of 5-HT (Ki = 0.5 nM) and stronger than those of the 5-HT agonist 5-MeO-DMT (Ki = 2.1 nM) or other ergot derivatives (bromocriptine and pergolide, Ki = 3.0 nM). Lisuride (0.1-0.5 mg/kg, i.p.), like 8-OH-DPAT, dose-dependently induced a 5-HT behavioral syndrome in rats. Lisuride affected locomotor activity in rats, whereas 8-OH-DPAT did not. In hippocampal EEG of rabbits, lisuride (0.01-0.03 mg/kg, i.v.), like 8-OH-DPAT and diazepam, dose-dependently inhibited rhythmical slow activity (RSA) induced by acoustical stimulation (3100 Hz) and also inhibited the RSA increased by administration of anxiogenic FG7142. In water-lick conflict tests, lisuride (0.05-0.1 mg/kg, i.p.), like diazepam, increased the number of shocks. These findings indicated that lisuride acts as a strong agonist on central 5-HT1A receptors and suggested that lisuride might be a potential anxiolytic.

Animals↗
PubMed1979

Suppression of prolactin secretion by lisuride throughout the menstrual cycle and in hyperprolactinaemic menstrual disorders.

Normally menstruating volunteers as well as patients with hyperprolactinaemic menstrual disorders were treated with lisuride hydrogen maleate (200 micrograms b.i.d.), an ergoline derivative with dopaminergic properties. Within 3 h after an oral dose of 200 micrograms lisuride, PRL levels decreased significantly in all subjects to a plateau which lasted up to 3 h. Thereafter a gradual increase of serum PRL was noted. In the normally menstruating volunteers lisuride treatment did not result in any significant change of gonadotrophin or of sex steroid secretion, while both, basal as well as metoclopramide (MTCL) stimulated PRL release were significantly diminished. The inhibition of PRL secretion in patients with short luteal phases resulted in an increase of luteal progesterone output. In both treated groups ovulation occurred 1 to 5 days earlier in cycles on lisuride than in control cycles. LF-RH/MTCL tests performed in the patient bearing a pituitary prolactinoma before and after lisuride treatment revealed a continuous increase of pituitary LH pools, while PRL secretion decreased under lisuride therapy. Subsequently ovulation and menstruation occurred. The data presented demonstrate that lisuride is a potent inhibitor of PRL secretion and has proven its clinical usefulness for treatment of hyperprolactinaemic menstrual disorders. Application of lisuride resulted in an increase of luteal progesterone secretion in previously demonstrated corpus luteum insufficiency as well as in restoration of normal cyclical feedback mechanisms in tumorous hyperprolactinaemic anovulation. The MTCL-PRL stimulation test is suitable to monitor PRL suppression during lisuride treatment, while LH-RH testing reveals the effectiveness of lisuride by demonstrating an increase of pituitary gonadotrophin pools.

Adenoma↗
PubMed1982

[Effects of an ergot derivative, lisuride, on the central dopaminergic system -- studies of behavioral pharmacology].

The central dopaminergic (DA) activity of lisuride hydrogen maleate (lisuride) was investigated from the view point of behavioral pharmacology in rats and mice. Lisuride exhibited a biphasic action on locomotor activity in mice and rats; with low doses lisuride caused hypomotility, whereas higher doses produced locomotor stimulation. The hypomotility induced by lisuride (0.00625 mg/kg, s.c.) was antagonized by a low dose of sulpiride (10 mg/kg, i.p.) in rats, and the lisuride (0.05 mg/kg)-induced hyperactivity was inhibited with haloperidol (0.1 mg/kg, i.p.). The stimulatory effect of lisuride on locomotion was not affected by the combined pretreatment with reserpine and alpha-methyl-p-tyrosine. The hyperactivity of mice induced by methamphetamine was inhibited by pretreatment with lisuride. In the rat lesioned unilaterally in the nigro striatal pathway by a local injection of 6-hydroxydopamine, a low dose of lisuride induced rotational behavior contralateral to the side of the lesion, and the rotational behavior was inhibited by pretreatment with haloperidol. These results indicate that lisuride at low doses effectively stimulates pre-synaptic DA receptors and the post-synaptic DA receptor under supersensitization in the mesolymbic and nigro striatal systems.

Animals↗
PubMed1985

Locomotor effects of lisuride: a consequence of dopaminergic and serotonergic actions.

The open-field test was used to study the involvement of serotonergic and dopaminergic mechanisms in the action of lisuride on locomotor activity in the rat. Lisuride produced a biphasic locomotor effect. The maximum locomotor stimulatory response of lisuride was stronger than that of apomorphine and comparable with that of apomorphine and LSD combined. Hypermotility induced by high doses of lisuride was partially suppressed by the serotonin antagonist cyproheptadine and not further enhanced by LSD. A moderate dose of lisuride potentiated apomorphine-induced hypermotility in the same manner as has been shown for LSD. Lesion of dopaminergic structures within the median raphe nucleus by 6-OHDA produced a potentiation of lisuride-induced hypermotility. This effect was suppressed by cyproheptadine. The locomotor inhibitory effect of low doses of lisuride may be related to a stimulation of presynaptic mesolimbic dopamine receptors. It is concluded that the locomotor stimulant effect of higher doses of lisuride may depend on stimulation of postsynaptic dopamine receptors and a serotonergic action and that the locomotor effects of lisuride reflect a complex interaction at dopaminergic and serotonergic transmission systems.

Animals↗
PubMed1978

Lisuride hydrogen maleate: evidence for a long lasting dopaminergic activity in humans.

In 12 acromegalics a single oral dose of 0.2 mg lisuride, an ergoline derivative, significantly reduced plasma PRL but not GH concentrations. Three-tenths milligram of the drug significantly reduced plasma levels of the two hormones. Four-tenths milligram of lisuride did not augment this inhibitory effect. Plasma PRL levels were suppressed in all patients, whereas GH levels were reduced by more than 50% of the base-line values in only seven patients who also responded to the administration of 2.5 mg bromocriptine (CB154). In the patients unresponsive to lisuride, CB154 also failed to change GH levels. The suppressive effect of lisuride started at 60 min (at 150 min for CB154) and plasma GH and PRL levels were still markedly suppressed at 300 min. Plasma GH and PRL concentrations were consistently reduced in two acromegalic patients during 2 weeks of chronic treatment with 0.3 mg lisuride four times a day. In six normal subjects, TRH-induced PRL release was significantly inhibited by pretreatment with 0.3 mg of the drug. The similarity in the effects of lisuride and CB154 suggests that the observed effects of lisuride on GH and PRL are attributable to the known dopaminergic activity of the drug. This conclusion is supported by the data showing that pimozide effectively counteracted the inhibitory action of lisuride on GH and PRL release. We suggest that lisuride may be of value in the medical treatment of acromegaly and hyperprolactinemic states.

Acromegaly↗
PubMed1982

[General pharmacology of lisuride hydrogen maleate--actions on isolated organs, especially on smooth muscles].

Pharmacological actions of lisuride hydrogen maleate (lisuride) were studied by using isolated organs. 1) Lisuride at 2.2 microM exerted a negative chronotropic effect on guinea-pig atria, the effect being antagonized completely by 2.9 microM sulpiride. 2) alpha-Adrenolytic action of lisuride was observed in the rat vas deferens and beta-adrenolytic action in the rabbit trachea, respectively. The former (ID50 = 64 nM) was potent and equivalent to that of phentolamine, whereas the latter (ID50 = 26 microM) was only 1/30 as compared to that of propranolol. 3) Anti-5-hydroxytryptamine action (ID50 = 11 nM) was detected in the rat stomach and anti-histamine (ID50 = 15 nM) in the guinea-pig ileum, respectively. In these respective activities, lisuride was equipotent to methysergide and diphenhydramine. 4) Lisuride showed a spasmodic action, which may be categolized as an ergot alkaloid action, on the guinea-pig ileum and on rabbit renal artery. A weak positive inotropic action of lisuride was also observed in guinea-pig atria. In the rat uterus, however, no uterotonic action of lisuride was detected. It is concluded that, in addition to its known effects on the central nervous system, lisuride possesses potent peripheral anti-5-hydroxytryptamine and anti-histamine activities.

Animals↗
PubMed1988

Effect of chronic subcutaneous minipump infusion of lisuride upon locomotor activity of rats.

Male Wistar rats were infused continuously for 14 days with lisuride 0.25 mg/kg/day or with vehicle via subcutaneously implanted osmotic minipumps. Locomotor activity was measured at 5 hours, 1, 7 and 14 days after implantation. Thereafter the minipumps were removed and 1, 7 and 21 days later the locomotor activity was recorded after a subcutaneous challenge dose of lisuride 0.1 mg/kg. In the course of continuous infusion the lisuride-treated rats showed a persistent stimulation of locomotor activity which remained almost constant throughout the whole period of exposure. At all intervals after removal of the minipumps lisuride challenge produced a less pronounced locomotor stimulation in lisuride-infused rats compared to vehicle-infused animals. This observation contrasts with the findings after chronic subcutaneous bolus treatment of rats with 0.25 mg/kg lisuride once daily for 29 days which resulted (1) in a progressive enhancement of the locomotor stimulatory effect and (2) in a longlasting hyperresponsiveness towards a subcutaneous challenge dose of lisuride 0.025 mg/kg. These results are discussed with respect to the advantage of the constant availability of lisuride at central dopamine receptors for the management of patients with advanced Parkinson's disease showing fluctuations in motor performance probably related to the kinetics of conventional oral therapy.

Animals↗
PubMed1989

[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↗
PubMed1989

[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↗
PubMed1987

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↗
PubMed1981

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↗
PubMed1982

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↗
PubMed1992

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↗