ergoline and Hypotension--Orthostatic

Lergotrile mesylate, an ergot alkaloid derivative and putative dopamine agonist, was effective in the majority of patients with Parkinson's disease who were showing signs of disease progression despite treatment with levodopa combined with a peripheral decarboxylase inhibitor (carbidopa). Among 20 patients completing a six-month trial, there was a significant (P less than .01) reduction in rigidity, tremor, bradykinesia, gait disturbance, and total score when lergotrile was added to levodopa plus carbidopa. Mean daily dose of lergotrile mesylate was 52 mg, and the mean daily dose of levodopa was reduced by 15%. Abnormal involuntary movements were decreased on addition of lergotrile and reduction in levodopa while mental changes and orthostatic hypotension were increased. Elevations in serum transaminase levels were noted in three patients. The ergot alkaloids promise to be an important new class of antiparkinsonian drugs.

Topics: Acetonitriles; Antiparkinson Agents; Bromocriptine; Carbidopa; Carboxy-Lyases; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Ergolines; Ergot Alkaloids; Female; Humans; Hypotension, Orthostatic; Levodopa; Male; Parkinson Disease

The hemodynamic and biochemical effects of cabergoline, a new ergoline derivative with selective, potent, and long-lasting dopamine (DA) agonistic properties, were evaluated in 19 parkinsonian patients, all previously identified as stable responders to levodopa plus L-Dopa decarboxylase inhibitor. The purpose of the study was to find markers capable of predicting the development of cardiopressor side effects during DA-agonistic therapy. Blood pressure (BP), heart rate, and plasma catecholamine responses to a standard meal and a tilt table test were evaluated before and during cabergoline therapy. Cabergoline (1.0 mg/day x os) in this open study significantly reduced the BP response to standing exclusively in the subgroup of patients who exhibited marked postprandial hypotension in baseline conditions. The patients subsequently experienced a partial recovery at day 7 of treatment. This finding indicates that postprandial hypotension is an early marker of autonomic failure in patients with Parkinson's disease (PD) and suggests the usefulness of evaluating cardiopressor response to a standard meal before starting new DA-agonist therapy in PD.

Topics: Aged; Blood Pressure; Cabergoline; Dopamine Agents; Ergolines; Female; Food; Heart Rate; Humans; Hypotension; Hypotension, Orthostatic; Male; Middle Aged; Parkinson Disease; Time Factors

8-alpha-amino-ergoline (CU 32-085) is a dopamine receptor agonist that should have fewer side effects than most other dopamine agonists. We studied the effect of this drug in 19 parkinsonian patients. In untreated or levodopa-treated patients, there was considerable improvement of akinesia, rigidity, and tremor; on-off symptoms also improved in the levodopa-treated patients. In patients pretreated with levodopa/bromocriptine, about half the dose of CU 32-085 was necessary to obtain the same therapeutic results, but there was no further improvement of on-off symptoms. Side effects were less pronounced than with bromocriptine; no circulatory disturbances and no psychotic episodes were observed.

Topics: Activities of Daily Living; Adult; Aged; Antiparkinson Agents; Bromocriptine; Drug Therapy, Combination; Ergolines; Female; Humans; Hypotension, Orthostatic; Levodopa; Male; Middle Aged; Nausea; Parkinson Disease; Psychomotor Performance; Receptors, Dopamine

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.

Topics: Adult; Aged; Cardiovascular System; Ergolines; Female; Heart Diseases; Heart Ventricles; Humans; Hypotension, Orthostatic; Male; Middle Aged; Myocardial Contraction; Parkinson Disease; Pergolide; Pulse; Sick Sinus Syndrome

Lergotrile mesylate is an ergot alkaloid derivative modified to eliminate the vasoconstrictive properties of the parent compound while preserving the properties that inhibit pituitary secretion. Administration of the drug to women with amenorrhea-galactorrhea resulted in the lowering of serum prolactin concentrations. The duration of action was short, so that prolactin levels were near base line 6 to 8 hours after a 2.0-mg dose and morning prolactin concentrations were not persistently suppressed. Initial therapy was accompanied by the development of postural hypotension. Tolerance to this side effect of the drug developed after several days of treatment with gradually increasing doses. In one patient, long-term treatment resulted in reduction of breast secretions, resumption of menses, and conception.

Topics: Acetonitriles; Adult; Amenorrhea; Ergolines; Female; Galactorrhea; Humans; Hypotension, Orthostatic; Lactation Disorders; Pregnancy; Prolactin

Bromocriptine in high doses (up to 100 mg per day) was administered to 14 patients with advanced Parkinson's disease whose disorder was progressing despite optimum treatment with levodopa combined with a peripheral dopa decarboxylase inhibitor (carbidopa). In 10, bromocriptine (mean dose, 57 mg) induced a statistically significant (P less than 0.01) improvement in rigidity, tremor, bradykinesia, gait disturbance and total score. In seven patients levodopa with carbidopa was completely replaced by bromocriptine (mean dose, 70 mg), with improvement in four. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance (on-off effect) were decreased whereas orthostatic hypotension and mental changes were increased. Bromocriptine appears to be a major new agent in Parkinson's disease that is especially promising in patients no longer responding to levodopa.

Topics: Aged; Bromocriptine; Delusions; Dopa Decarboxylase; Drug Evaluation; Ergolines; Female; Humans; Hypotension, Orthostatic; Levodopa; Male; Middle Aged; Parkinson Disease