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At least 19 recordsLinked to original sources
PubMed1983

Microbial transformations of pergolide to pergolide sulfoxide and pergolide sulfone.

Fifty-eight microorganisms were investigated for their ability to effect the biotransformation of the ergoline alkaloid pergolide. A majority of these organisms formed pergolide sulfoxide, and a Helminthosporium species was investigated in greater detail since it yielded significant amounts of pergolide sulfoxide. A preparative-scale transformation afforded material which was identified as the sulfoxide based on melting point, spectral, and chromatographic comparison with authentic material as well as its conversion to pergolide by reduction with triphenylphosphine. An analytical high-performance liquid chromatographic determination of the enzymatic versus spontaneous air-oxidation of pergolide in growing cultures and controls showed negligible air-oxidation and an approximately 40% enzymatic conversion of pergolide to the sulfoxide. Several organisms, including Aspergillus alliaceus formed a second metabolite, pergolide sulfone, which was identified on the basis of co-chromatographic data.

Aspergillus↗
PubMed1981

Repeated administration of pergolide to rats attenuates the acute elevation of serum corticosterone by pergolide.

A single injection (0.3 mg/kg IP) of pergolide mesylate, a dopamine agonist, increased serum corticosterone concentration several-fold in rats. This increase did not occur or was greatly diminished in rats that had received four previous daily injections of pergolide. The non-responsiveness to pergolide persisted at the second day after the last of 4 daily injections of pergolide, but by the third and fourth days the rats were again responsive to pergolide in terms of serum corticosterone elevation. The lowering of dopamine metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) by pergolide occurred in pergolide-pretreated rats to the same extent as in control rats. Serum corticosterone concentration in pergolide-pretreated rats was elevated normally by a serotonin agonist, quipazine. Since the pituitary-adrenocortical system can be activated in pergolide-pretreated rats (indicated by the normal response to quipazine), the insensitivity to pergolide may be due to decreased responsiveness of central dopamine receptors mediating corticosterone elevation by pergolide.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Pharmacological, hemodynamic and biochemical mechanisms involved in the blood pressure lowering effects of pergolide, in normotensive and hypertensive dogs.

In pentobarbital-anesthetized normotensive dogs, clonidine (20.0 micrograms/kg i.v.), in contrast to pergolide (30.0 micrograms/kg i.v.), reduced significantly both aortic blood pressure and plasma concentration of norepinephrine. However, in dogs that had been made hypertensive by sectioning the vagi and carotid sinus nerves, pergolide, like clonidine, lowered the blood pressure and plasma concentrations of epinephrine and norepinephrine that were enhanced markedly by deafferentation. Furthermore, in this preparation pergolide decreased the calculated resistance in vascular regions supplied by the upper abdominal aorta and the innervated femoral and renal arteries, but it increased vascular resistance in the denervated hind leg. Pergolide (1.0 microgram/kg) injected intracisternally (i.c.m.) induced a fall in blood pressure of comparable magnitude to that produced by a 30 times higher i.v. dose. Intravenously and i.c.m. administered pergolide lowered blood pressure by acting at distinct anatomical sites inasmuch as i.v. sulpiride blocked the effects of i.v. but not i.c.m. pergolide. The combination of sulpiride plus yohimbine injected i.c.m. was necessary to abolish the decrease in blood pressure evoked by i.c.m. pergolide. In atropinized spinal dogs, i.v. pergolide inhibited the vasoconstriction elicited by electrical stimulation of the lumbar sympathetic chain, an effect which was antagonized by sulpiride. Similarly, pergolide (30.0 micrograms/kg i.v.) like clonidine, reduced the heart rate and coronary venous plasma norepinephrine concentration raised by sustained electrical stimulation of the cardioaccelerator nerve. Sulpiride, but not phentolamine, antagonized this pergolide-induced inhibition of sympathetic nerve function. In chlorisondamine-pretreated dogs, pergolide produced a transient pressor response due to stimulation of postsynaptic vascular alpha-2 adrenoceptors. In conclusion, the failure of i.v. pergolide to decrease aortic blood pressure in pentobarbital-anesthetized normotensive dogs is presumably due to the inability of pergolide to produce a significant inhibition of the vascular sympathetic tone in this preparation. However, in neurogenic hypertensive dogs which are characterized by an elevated level of sympathetic drive, i.v. pergolide reduced blood pressure and aortic plasma norepinephrine concentration. These effects of pergolide are compatible with a DA-2 dopamine receptor stimulation on peripheral sympathetic nerve fibers. In contrast, the antihypertensive effects of i.c.m. pergolide would appear to be mediated by both alpha-2 adrenoceptors and DA-2 dopamine receptors located within the central nervous system.

Anesthesia↗
PubMed1983

Central and peripheral dopaminergic mechanisms in the cardiovascular actions of pergolide in neurogenic hypertensive dogs.

The cardiovascular actions of the dopaminergic ergoline, pergolide were examined in pentobarbital-anesthetized dogs. When administered intravenously (i.v.) to dogs made hypertensive by sino-aortic deafferentation, pergolide produced a sustained reduction in blood pressure, dilatation of the hindlimb vasculature and bradycardia. The antihypertensive action of pergolide in neurogenic hypertensive dogs was converted into a pressor action when it was given to dogs pretreated with i.v. sulpiride or hexamethonium plus atropine. Pergolide caused significant impairment of renal vasoconstriction elicited during stimulation of renal sympathetic nerves but not that caused by exogenous norepinephrine. The inhibitory action of pergolide on renal sympathetic nerve function was antagonized by sulpiride suggesting that pergolide activated presynaptic dopamine receptors. Direct administration of pergolide within the central nervous system via the cisterna magna (i.c.) to normotensive dogs also resulted in hypotension, bradycardia and iliac vasodilatation. The central actions of pergolide were prevented by sulpiride (i.c.) but not by yohimbine (i.c.), which indicates that specific activation of central dopamine receptors was responsible for these actions of pergolide. The antihypertensive, bradycardic and iliac vasodilatory actions of i.v. pergolide in neurogenic hypertensive dogs were significantly attenuated by i.c. sulpiride. It was determined that while this dose of sulpiride antagonized central dopamine receptors, it did not antagonize peripheral presynaptic dopamine receptors. These results suggest that pergolide exerts antihypertensive and bradycardic actions via simultaneous stimulation of dopamine receptors in the brain and on postganglionic sympathetic neurons. While presynaptic dopamine receptor activation contributes to the blood pressure lowering action of pergolide, stimulation of central dopamine receptors appears to be the dominant mechanism by which pergolide elicits the observed antihypertensive and bradycardic effects. Pergolide appears to lower blood pressure by a novel mechanism of action and may offer an additional therapeutic approach for the treatment of hypertension.

Animals↗
PubMed1981

Pergolide mesylate: its effects on circulating anterior pituitary hormones in man.

Pergolide mesylate is a synthetic ergoline with dopamine agonist properties. The endocrine profile was studied in a double blind crossover design in six normal males. Circulating PRL, TSH, GH, LH, FSH, and cortisol were measured in the basal state and after TRH (500 micrograms iv) administration at 4.5, 11.5, and 23.5 h after placebo or pergolide (100 micrograms orally). Pergolide caused suppression of basal PRL from 2-8 ng/ml to less than 2 ng/ml commencing 60 min after administration and persisting throughout the 23.5-h study period. For the three TRH tests, a suppression of peak PRL (mean +/- SEM) response to TRH of 54.6 +/- 5.1 vs. 1.9 +/- 0.5, 45.2 +/- 4.1 vs. 4.5 +2- 0.6, and 34.4 +/- 2.9 vs. 6.9 +/- 1.4 ng/ml, respectively, for placebo and pergolide was noted. Basal TSH levels were unaffected by pergolide, but after pergolide the peak TSH response to the first two TRH challenges was blunted (placebo vs. pergolide: 12.3 +/- 1.2 vs. 6.8 +/- 1.0 and 14.8 +/- 2.0 vs. 9.6 +/- 1.0, respectively); however, the third TSH response (9.8 +/- 1.1 vs. 9.3 +/- 1.2) was not blunted after pergolide. GH secretion was stimulated by pergolide with a consistent pulse observed within 60 min of pergolide administration and an enhancement in the number and amplitude of subsequent GH pulses throughout the 24-h period. Cortisol levels rose after pergolide and returned to levels seen on the control day at 16.5 h. FSH levels were unaffected but LH levels were lowered pergolide. Side effects including nausea, vomiting, and hypotension were observed in all subjects. Pergolide is a potent dopamine agonist with the anticipated endocrine profile and clinical effects; its long duration of actions offers promise of single daily dose therapy for hyperprolactinemia.

Adult↗
PubMed1984

Pharmacological, hemodynamic and autonomic nervous system mechanisms responsible for the blood pressure and heart rate lowering effects of pergolide in rats.

In conscious spontaneously hypertensive rats, pergolide (50.0 micrograms/kg s.c.) produced a sustained decrease in tail artery pressure which was blocked by haloperidol (1.0 mg/kg s.c.) pretreatment. In anesthetized spontaneously hypertensive rats this effect was accompanied by a fall in total peripheral resistance inasmuch as pergolide did not significantly change cardiac output. In anesthetized normotensive rats, pergolide (30.0 micrograms/kg i.v.) also lowered blood pressure. This effect was not significantly modified by adrenalectomy, methysergide, idazoxan (alpha-2 adrenoceptor antagonist), vagotomy alone or plus ligation of carotid arteries or plus atenolol, but was entirely prevented by domperidone or sulpiride pretreatment and was reverted to a pressor response (due to stimulation of alpha adrenoceptors and 5-hydroxytryptamine receptors) by blockade of ganglionic transmission with chlorisondamine. Pergolide given either i.v. or into the cisterna magna or the lateral cerebral ventricle produced changes in blood pressure of the same magnitude. In intact or adrenalectomized rats, i.v. pergolide significantly lowered plasma norepinephrine concentration. Furthermore, in saline but not sulpiride-pretreated pithed rats, pergolide reduced the pressor responses and the accompanying increases in plasma norepinephrine evoked by electrical stimulation of the spinal cord. However, pergolide failed to modify the vascular reactivity to several pressor agents and lacked beta-2 and DA-1 dopamine receptor agonist properties. These results indicate that the decrease in blood pressure produced by pergolide can be accounted for by an inhibition of sympathetic tone resulting from stimulation of peripheral neuronal dopamine receptors. A possible central contribution remains to be substantiated. The pronounced bradycardia produced by pergolide (30.0 micrograms/kg i.v.) in anesthetized intact rats was partly reduced by vagotomy, methylatropine, domperidone, sulpiride, idazoxan, phentolamine or atenolol. The effects of pergolide in vagotomized rats were further diminished by domperidone but they were blocked by the combination of phentolamine or idazoxan plus domperidone. In rats pretreated with atenolol or in rats with the cervical section of spinal cord and the low level of heart rate increased with an isoprenaline infusion, the decrease in heart rate produced by pergolide was abolished by domperidone, methylatropine or idazoxan. In pithed rats, pergolide changed neither the base-line heart rate nor the tachycardia to exogenous norepinephrine nor the bradycardia evoked by carbachol or electrical stimulation of the peripheral cervical vagus.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1985

Behavioral effects of pergolide mesylate on food intake and body weight.

In a crossover design experiment, pergolide mesylate significantly suppressed food intake and body weight in spayed female rats. Inhibition of food intake by a constant dose of pergolide progressively diminished with repeated administrations. Pergolide continued to suppress body weight with no indications of tolerance. When pergolide was discontinued, body weight increased sufficiently to compensate for the loss and failure to gain during drug treatment. A second experiment investigated the observation that animals injected first with vehicle showed greater anorexia when subsequently injected with pergolide than did animals injected first with pergolide. In addition, tolerance was further assessed by administering on two occasions a higher dose of pergolide. Following chronic pergolide treatment, this dose was insufficient to reinstate anorexia; however, after a period of abstinence, this dose produced anorexia comparable to that observed at the beginning of pergolide treatment. Due to pergolide mesylate's action as a postsynaptic dopamine agonist, a dopaminergic neural system is implicated in pergolide induced anorexia.

Animals↗
PubMed1992

Behavioral characterization of the new potent nonselective dopamine agonist pergolide.

Pergolide (LY127809, CAS 66104-23-2), a non-selective dopamine agonist, was evaluated for broad behavioral properties in a wide range of pharmacological tests. The selective dopamine2(D2) agonist, bromocriptine, served as a reference standard for those tests where behavioral activity was noted with pergolide. Pergolide and bromocriptine were administered orally to mice at doses of 0.3-30 and 3-300 mg/kg, respectively. Both compounds produced biphasic effects on spontaneous activity, increased hexobarbital-induced sleep time, and lowered mouse body temperature. Qualitative changes with pergolide were observed with some mice showing hyporeactiveness, ptosis, slowed respiration and placing loss. Reserpine-induced hypothermia was reversed by pergolide with significant increases in the body temperature of reserpine-treated mice. However, a further reduction in the body temperature of reserpinized hypothermic mice was seen following bromocriptine administration. Acetic acid-induced writhing and performance on the rotarod were both impaired by higher doses of pergolide. Bromocriptine administration also reduced writhing at higher doses but did not alter performance on the rotarod. Pergolide had no effect on seizure activity as evaluated by electroshock, pentylenetetrazol (pentetrazol) or strychnine. Oxotremorine-induced tremors and salivation, grip strength, and tail-flick were not affected by pergolide. Neither pergolide nor bromocriptine altered established shuttle-avoidance behavior in rats at oral doses of 0.1 to 30 mg/kg. Behavioral assessment of pergolide in dogs was complicated by severe emetic responses at clinically relevant doses greater than 0.003 mg/kg. In summary, these data suggest that pergolide produces a behavioral profile which is characteristic of dopaminergics.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1991

Anti-inflammatory activity of pergolide, a dopamine receptor agonist.

Pergolide, a dopamine agonist effective in the treatment of Parkinson's disease, has been shown to have anti-inflammatory activity in the carrageenan paw edema assay in rats at p.o. doses greater than or equal to 0.3 mg/kg. Studies were done to investigate the mechanism of action and to determine the pharmacologic significance of this finding. Because pergolide elevates circulating glucocorticoids, the effect of pergolide on carrageenan-induced paw swelling was assessed in adrenalectomized rats. Pergolide retained its anti-inflammatory activity in adrenalectomized carrageenan-injected rats, thus eliminating corticosterone induction as a possible mechanism of action. Pergolide treatment also did not decrease thromboxane B2, prostaglandin E2 or leukotriene B4 production, ruling out direct effects on arachnoid acid inflammatory mediators. Interactions with the autonomic nervous system were suggested, in that an alpha adrenergic agonist (clonidine) mimicked the activity of pergolide in the carrageenan assay, and an alpha adrenergic antagonist (phenoxybenzamine) blocked the anti-inflammatory activity of pergolide in this assay. Dopamine receptor antagonists (haloperidol or sulpiride) partially inhibited the effect of pergolide in the carrageenan model. However, the peripherally restricted dopamine antagonist, domperidone, was ineffective, suggesting that a central dopamine receptor was involved in the effect. Experiments in chronic inflammation models such as lipoidal-amine induced arthritis in rats and picryl chloride-induced delayed type hypersensitivity in mice also revealed an anti-inflammatory effect of pergolide. Activity in the carrageenan system and the lipoidalamine model demonstrated that the anti-inflammatory effects of pergolide were separable from potential immunosuppressive effects. Multiple dose studies indicated that tolerance might develop to the anti-inflammatory effect of pergolide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Characterization of the neurogenic vasodilatation elicited by central dopamine receptor stimulation with pergolide.

In the present study, we have employed the procedure of bilateral hindlimb perfusion at controlled flow rates to investigate centrally mediated actions of the dopamine receptor agonist pergolide on hindlimb vascular resistance in anesthetized dogs. Intracisternal administration of pergolide caused sustained hypotension, bradycardia and a decrease in perfusion pressure in the innervated hindlimb, whereas perfusion pressure in the denervated limb was not altered by pergolide. In addition, the pressure-flow curves were shifted to the right in the innervated hindlimb but not in the denervated limb, suggesting that pergolide caused neurogenic dilatation in the hindlimb vasculature. Intravenous administration of the same dose of pergolide elicited transient hypertension and marked vasoconstriction in the denervated limb. Hypotension and neurogenic hindlimb vasodilatation of lesser magnitude than that produced by intracisternal pergolide were seen only 40 to 50 min after administration of i.v. pergolide. The hindlimb vasodilator action of intracisternal pergolide could be antagonized by sulpiride, which suggests that activation of central dopamine receptors was responsible for the action of pergolide. Because the neural innervation to the hindlimb is comprised of sympathetic vasoconstrictor as well as cholinergic and dopaminergic vasodilator fibers, additional experiments were performed to determine the mechanisms involved in the neurogenic vasodilatation caused by pergolide. Treatment with atropine did not alter the neurogenic decrease in the hindlimb vascular resistance produced by pergolide, indicating that activation of cholinergic vasodilator fibers was not responsible for this phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Differential effects of quinelorane and pergolide on behaviour, blood pressure, and body temperature of spontaneously hypertensive rats and Wistar-Kyoto rats.

The systemic administration of the dopamine agonists quinelorane or pergolide to Wistar-Kyoto rats (WKY) induced a significant increase of locomotor activity at higher doses. In spontaneously hypertensive rats, these compounds induced a significant hypoactivity at low doses, but only a modest, and late, increase in locomotor activity at higher doses. Quinelorane was more potent than pergolide on locomotor activity. In WKY and SHR, which had unilateral lesions of the nigrostriatal dopamine system, quinelorane and pergolide induced similar dose-dependent contralateral turning that, in the case of pergolide, was significantly greater in SHR than in WKY. Both quinelorane and pergolide induced yawning similarly in WKY and SHR, and quinelorane was more potent than pergolide. The intravenous administration of quinelorane induced an immediate and dose-dependent increase in blood pressure in WKY and SHR, which could be completely prevented by pretreating the rats with the dopamine antagonist haloperidol. Pergolide similarly caused a rise in blood pressure in WKY and SHR, but its effect could only partially be blocked by haloperidol. The subcutaneous injection of quinelorane or pergolide induced similar dose-dependent hypothermia in WKY. Pergolide also caused a decrease of body temperature in SHR, but quinelorane had little effect in this strain. These results show differences in the effects of quinelorane and pergolide between various experimental test situations and between WKY and SHR. These differences may be related to the involvement of dopamine receptor subtypes and to the previously described changes in central dopaminergic activity in SHR.

Animals↗
PubMed1995

A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson's disease.

A single-blind, crossover study was carried out to compare the efficacy and safety of pergolide against that of bromocriptine in 57 patients with Parkinson's disease who showed a declining response to levodopa therapy. Patients were randomly assigned to receive either bromocriptine followed by pergolide, or pergolide followed by bromocriptine. Both drugs were administered for 12 weeks. Patients were assessed by a clinician blinded to treatment assignment using the New York University Parkinson's Disease Scale. The average daily dose of pergolide was 2.3 +/- 0.8 mg and of bromocriptine 24.2 +/- 8.4 mg. Addition of pergolide or bromocriptine resulted in a significant improvement in total scores when compared with the previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005). Pergolide was more effective than bromocriptine in daily living scores (p = 0.02) and motor scores (p = 0.038). No differences in the incidence of dyskinesias, dystonias, or psychosis were observed between groups. Fewer adverse events were recorded in the pergolide group, and most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.

Aged↗
PubMed1993

Dopamine receptor affinities in vitro and neurochemical effects in vivo of pergolide and its metabolites.

Pergolide (LY127809, CAS 66104-23-2), pergolide sulfone and pergolide sulfoxide inhibited 3H-dopamine binding to dopamine receptors in bovine striatal membranes with Ki values of 2.5, 4.6 and 15.5 nmol/l, respectively. Despropyl pergolide and despropyl pergolide sulfoxide are not as potent, with Ki values of 58.6 and 158.8 nmol/l, respectively. The derivatives of pergolide inhibit the binding of antagonist ligands 3H-Sch23390 and 3H-Spiperone to D1 and D2 dopamine receptors, respectively, in bovine striatal membranes with higher Ki concentrations. Upon administration to rats, pergolide sulfoxide and sulfone were as effective as pergolide in increasing acetylcholine levels and decreasing the metabolites of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in striatum, while the despropyl derivatives of pergolide and pergolide sulfoxide were only marginally effective in increasing acetylcholine levels in striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged-Fischer-344 rats.

Pergolide, a potent D2 presynaptic agonist with postsynaptic D2 agonist activity and some D1 agonist activity was administered in the diet (0.5 mg/kg/day) of male Fischer 344 rats from age 3 to age 26 months. We hypothesized that the potent D2 presynaptic activity would reduce the baseline release of dopamine (DA) and thereby slow the formation of toxic oxidative metabolites that lead to age-related deterioration of nigrostriatal DA neurons. Pair-fed rats served as controls. We observed age-related losses of fluorescent DA cell bodies in the substantia nigra pars compacta and of fluorescent DA terminals in the striatum; chronic pergolide administration prevented these losses. Pergolide administration also prevented the age-related diminution of DA fluorescence intensity in substantia nigra cell bodies. A large decline in 3H-DA uptake with age was partially prevented by pergolide administration. We found no age-related alteration in the concentration of DA in the striatum and pergolide did not alter this concentration. Pergolide treatment resulted in only minor alterations in striatal 3H-spiperone binding and no change in dendritic arborizations of either DA substantia nigra neurons or medium spiny striatal neurons. Pergolide administration also prevented an age-related decline in circulating FSH levels. The uptake data and quantitative morphological findings suggest that pergolide administration in the diet for 2 years exerts a protective effect on age-related deterioration of DA nigrostriatal neurons. This finding was consistent with clinical reports of a subset of patients with Parkinson's disease in whom long-term efficacy of pergolide therapy is observed.

Aging↗
PubMed1988

Pergolide: long-term use in Parkinson's disease.

Previous short-term studies have shown that the dopamine agonist pergolide improves control of Parkinson's disease when used in conjunction with carbidopa-levodopa (Sinemet). We assessed the long-term outcome (2 1/2- to 3-year follow-up) in patients with Parkinson's disease who participated in our previous pergolide double-blind trial and were subsequently switched to open-label pergolide therapy. Of 41 evaluable patients who began pergolide therapy, 10 (24%) experienced sustained substantial benefit that persisted to the end of this investigation. A total of 23 patients (56%) remained on pergolide therapy and, as a group, had considerable improvement over baseline at 2 1/2 to 3 years on the basis of several measurements of efficacy. A tendency toward deterioration could be reversed in many patients by larger or more frequent doses of carbidopa-levodopa; nevertheless, all but four patients were still taking the same dose or less of carbidopa-levodopa at the end of this study as at the onset. Patients with the best initial response to pergolide seemed most likely to experience long-term benefit. Confusion and hallucinations were the side effects most likely to necessitate discontinuation of pergolide. Symptoms suggestive of dose-related angina pectoris occurred in four patients in the open-label phase and two patients in the earlier double-blind phase (13% of patients who started pergolide therapy); these symptoms were easily controlled by dose reduction or discontinuation of pergolide, without sequelae. Dose-related leukopenia developed in one patient.

Aged↗
PubMed1983

Elevation of serum corticosterone in rats by dopamine agonists related in structure to pergolide.

Two chemical analogs of pergolide were examined to test further the idea that pergolide elevates serum corticosterone concentration in rats by activation of brain dopaminergic receptors. LY116467, which contains an N-methyl substituent in place of the N-n-propyl substituent in pergolide, was less potent than pergolide in lowering brain levels of 3,4-dihydroxyphenylacetic acid (Dopac), the metabolite of dopamine. LY116467 increased serum corticosterone concentration in rats at a dose of 3 mg/kg (a higher dose than is required for pergolide), and the effect was prevented by spiperone pretreatment. LY141865, which has been reported to differ from pergolide in not activating dopamine-sensitive adenylate cyclase and which was found in this study to have much less affinity for serotonin receptors than does pergolide, increased serum corticosterone in much the same manner as pergolide, only slightly higher doses being required. The effect of LY141865 was prevented by pretreatment with haloperidol but not domperidone. Both haloperidol and domperidone increased serum prolactin concentration when given alone or in combination with LY141865, indicating they were both capable of blocking peripheral (pituitary) dopamine receptors. In contrast, haloperidol but not domperidone caused a marked elevation in brain levels of Dopac and of homovanillic acid and prevented the lowering of these brain dopamine metabolites by LY141865. The ability of LY141865 to increase serum corticosterone concentration was attenuated in rats that had received four daily injections of pergolide mesylate, indicating corss-tolerance had occurred. These results strengthen the hypothesis that activation of brain dopaminergic receptors leads to increased serum corticosterone concentration in rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

The effects of pergolide on the cardiovascular system of 40 patients with Parkinson's disease.

The effect of pergolide, a semisynthetic ergot alkaloid, on the cardiovascular system of 40 patients with Parkinson's disease (PD) was evaluated. The mean daily dose of pergolide was 2.4 mg (range, 0.1 to 10 mg). The mean duration of follow-up was 6 months (range, 2 weeks to 20 months). The 40 patients were selected only on the basis of severe PD. All 13 patients in the first part of the study underwent 1 to 5 days of Holter monitoring before starting pergolide. Monitoring was then carried out for an additional period of between 2 and 10 weeks while the patients were on pergolide. Seven of the 13 patients manifested repetitive ventricular rhythms. These were isolated and unassociated with increases in premature ventricular contractions. The dose at which the RVRs occurred was a function of the presence or absence of heart disease. The changes occurred below 3 mg/day in patients with heart disease and above 3 mg/day in patients without heart disease. Pergolide was discontinued in three of the patients with heart disease. It was concluded that pergolide may, in the diseased heart, predispose to RVRs. In the second part of the study, Holter monitoring was carried out only at the discretion of the cardiologist, and five patients were so monitored. None of these patients was rejected from the study. Only one patient (with heart disease) of the 27 patients in the second part of the study experienced an arrhythmia. This consisted of an increase in PVCs on 4 mg/day of pergolide. Pergolide was discontinued. Eight of the 40 patients in these early dose-ranging studies experienced orthostasis, two with syncope, immediately on addition of pergolide (0.1 to 0.4 mg) to levodopa. The orthostasis could be eliminated in all but two patients by reducing or discontinuing levodopa.

Adult↗