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PubMedDate not supplied

Pergolide in the treatment of patients with early and advanced Parkinson's disease.

Introduced on the market in 1989, pergolide, a D1/D2 dopamine receptor agonist, is still widely prescribed for the treatment of patients with early and advanced Parkinson's disease (PD). Initially, pergolide was introduced as an adjunct therapy to levodopa treatment in patients exhibiting fluctuating motor responses and dyskinesias. Results of recent randomized controlled clinical trials in de novo patients with PD show that pergolide is able to improve parkinsonian symptoms when used as monotherapy. Moreover, preliminary results of a long-term monotherapy study in early PD suggest that pergolide is as effective as levodopa, and that a significant delay in the time of the onset of levodopa-induced motor complications can be obtained. A number of randomized studies have shown that pergolide is more effective than bromocriptine as adjunct therapy to levodopa in patients with advanced PD; the greater benefit found with pergolide could be ascribed to its action on both D1 and D2 dopamine receptors. However, controlled comparative studies with new dopamine agonists, such as ropinirole, cabergoline, and pramipexole, have not been performed yet. Interestingly, few open studies in patients with complicated PD have shown that high doses of pergolide (> 6 mg/d) are able to improve motor fluctuations and dyskinesias through a dramatic reduction of levodopa dosage. The side-effect profile of pergolide is similar to that of other dopamine agonists, and complications such as sleep attack and serosal fibrosis have been rarely reported.

Antiparkinson Agents↗

PubMed1991

A comparison of the efficacy and safety of pergolide and bromocriptine in the treatment of hyperprolactinemia.

UNLABELLED: Pergolide is a synthetic ergoline derivative with highly potent long-acting PRL-lowering activity, allowing therapy of hyperprolactinemia with a once daily administration of the drug. The results of two open-label, randomized controlled multicenter clinical trials are reported. Pergolide (taken once a day), was compared with bromocriptine (taken two to four times daily) regarding efficacy and safety in the reduction of PRL levels, the cessation of galactorrhea and amenorrhea, the improvement in sexual function, and tumor shrinkage in hyperprolactinemia without (trial I; 61 patients) and with radiologically evident pituitary tumors (trial II; 96 patients). Both drugs were equally effective in lowering PRL levels in both trials. A median optimal dose of 50 micrograms pergolide and 5 mg bromocriptine/day suppressed PRL levels in the 61 patients of trial I by more than 80%. During the 24-week investigational period galactorrhea disappeared in 96% and 87% of patients, whereas menstruation returned in 90% and 96% of patients, respectively. An equally high efficacy (optimal median dose: 75-100 micrograms pergolide, 7.5-10 mg bromocriptine daily) was observed in trial II, although the resumption of menses was less frequent than in the patients of trial I (50% and 58% of patients, respectively). Sexual dysfunction improved similarly on both drugs in about half the patients. In addition, tumor shrinkage occurred to a similar extent with both drugs. A high incidence of adverse events was noted especially at the initiation of therapy with both compounds: nausea, dizziness, vomiting, asthenia, headache, and decrease in blood pressure occurred at a similar incidence and extent during the use of pergolide and bromocriptine. Patients in trial I treated with pergolide reported a slightly higher incidence of fever, vasodilatation, and flu syndrome. CONCLUSIONS: in these 24-week studies comprising a total of 157 hyperprolactinemic patients, a once daily administration of pergolide was shown to be as safe and effective as the two to four times daily ingestion of bromocriptine. Longer-acting dopamine agonists like pergolide that can be taken once daily, are likely to increase the ease to adherence to the therapeutic regimen. This might result in a higher compliance to medical treatment of hyperprolactinemia.

Adult↗

PubMed2004

Pergolide use in Parkinson disease is associated with cardiac valve regurgitation.

OBJECTIVE: To determine if pergolide injures heart valves, by comparing echocardiographic findings in pergolide-treated patients with those of a historical control group. METHODS: Letters were sent to all patients in the authors' practice believed to be taking pergolide, and those responders who wished to continue it were urged to undergo echocardiography. Echocardiograms were obtained on 46 patients, and scores for valvular regurgitation were compared with those from an age-matched control group derived from the Framingham Study. The composite valve regurgitation score was modeled as a linear function of total milligrams lifetime use of pergolide, controlling for age. RESULTS: Eighty-nine percent of pergolide-treated patients had some degree of valvular insufficiency. For each of the three valves for which there are control data, we found an approximately 2- to 3-fold increased risk of abnormal valves in the pergolide patients (odds ratio [OR] approximately 3) and an estimated 14-fold increased risk of concerning tricuspid regurgitation (OR = 18.4). The composite valve score (the sum of valve scores for each of the four valves) was a function of lifetime pergolide use. CONCLUSION: Pergolide may injure cardiac valves, resulting most commonly in tricuspid regurgitation.

Aged↗

PubMed1990

Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease.

When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options.

Animals↗

PubMed2004

Pergolide, terguride and N,N'-spacer-linked oligomers of both interact with 5-HT2A receptors of rat tail artery.

Pergolide, terguride and N,N'-spacer-linked oligomers of both have been tested for their ability to interact with 5 hydroxytryptamine(HT)2A receptors of rat tail artery. Pergolide was a potent partial agonist (pEC50 7.5, Emax 55 %) and antagonized 5-HT-induced contractions (pKp 7.2). Pergolide dimer 3 with a p-xylene spacer between the indole nitrogens (N-1) displayed somewhat lower agonist potency than pergolide (pEC50 7.0, Emax 55 %, pKp 6.6). The contractile responses to pergolide and dimer 3 were antagonized by the 5-HT2A receptor antagonist ketanserin (pA2 9.4, 9.1). In contrast to pergolide dimer 3, pergolide dimers 5 and 9 with an alkyl and an aralkyl spacer between the piperidine nitrogens (N-6) lacked agonism and displayed low affinity at 5-HT2A receptors (pA2 < 5.5). Terguride behaved as an insurmountable antagonist of 5-HT (pA2 8.4). Oligomers of terguride showed 5 to 50-fold lower affinity. It is concluded that pergolide and terguride show a high affinity for 5-HT2A receptors, but dimerization (oligomerization) of both drugs fails to increase affinity.

Animals↗

PubMed1993

Dopamine agonist activities of pergolide, its metabolites, and bromocriptine as measured by prolactin inhibition, compulsive turning, and stereotypic behavior.

Four pergolide metabolites and bromocriptine (CAS 25614-03-3) were compared to pergolide (8 beta-[(methylthio) methyl]-6-propyl-ergoline, CAS 66104-22-1) using three in vivo animal models of activity at dopamine receptors. The results obtained from these studies of prolactin inhibition, induction of compulsive turning, and stimulation of stereotypic behavior, were very consistent. Two of the metabolites, despropyl pergolide and despropyl pergolide sulfoxide, were devoid of dopamine-like effects in any of the models. Pergolide sulfone and pergolide sulfoxide, however, were found to be potent dopamine agonists, similar in activity to pergolide itself. Dopamine D2 receptors (and probably D1 receptors also) appear to be involved in the activities of these compounds. The compounds were active by both oral and i.p. routes of administration. Bromocriptine, while possessing some dopamine agonist activity at higher doses in some of these animal models, was much less potent (1/200 to 1/20) than either pergolide or its two dopaminergic metabolites.

Administration, Oral↗

PubMed2006

Pergolide versus levodopa monotherapy in early Parkinson's disease patients: The PELMOPET study.

Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complications. This paradigm is based on long-term studies, allowing "rescue" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the pergolide-versus-L-dopa-monotherapy-and-positron-emission-tomography trial) evaluated the efficacy and safety of pergolide versus levodopa without levodopa "rescue" medication. This multicenter, double-blind, randomized, 3-year trial compared pergolide monotherapy (n=148) with levodopa monotherapy (n=146) in dopamine-naive patients with early PD (Hoehn and Yahr stage 1-2.5). Primary efficacy measures were clinical efficacy, severity and time to onset of motor complications, and disease progression. During the 3 years, severity of motor complications was significantly lower and time to onset of dyskinesia was significantly delayed in the group receiving pergolide (3.23 mg/day) compared with those receiving levodopa (504 mg/day). However, time to onset of motor complications was not longer in patients receiving pergolide after 3 years. Symptomatic relief (assessed by Unified Parkinson's Disease Rating Scale [UPDRS], UPDRS II, and III, Clinical Global Impressions [CGI] severity, and CGI and Patient Global Impressions [PGI] improvement) was significantly greater in patients receiving levodopa. Adverse events led to discontinuation of therapy in 17.6% of pergolide patients and 9.6% of levodopa patients. This is the first study comparing strict monotherapy with a dopamine agonist versus levodopa in previously untreated early PD. In principle, both levodopa and a dopamine agonist such as pergolide seem to be suitable options as initial PD therapy. The choice remains with the treating physician based on the different efficacy and adverse event profiles.

Adult↗

PubMed1994

Pergolide compared with bromocriptine in Parkinson's disease: a multicenter, crossover, controlled study.

We compared the efficacy and safety of pergolide and bromocriptine in 57 patients with Parkinson's disease (PD) with a declining response to levodopa therapy in a single-blind, crossover study. Patients were placed randomly on the sequence bromocriptine-pergolide (12 + 12 weeks) or vice versa. Regular evaluations using the New York University Parkinson's Disease Scale were performed by a clinician blinded to treatment assignment. Patients' and clinicians' impressions also were recorded. The average daily dose of pergolide was 2.3 +/0- 0.8 mg, and that of bromocriptine was 24.2 +/- 8.4 mg. Significantly greater efficacy was demonstrated by both drugs as adjunctive therapy to levodopa compared with previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005; Wilcoxon t test). Pergolide was more effective than bromocriptine in daily living scores (p = 0.020) and motor scores (p = 0.038). No difference in dyskinesias, dystonias, and psychosis was observed. Adverse events were more frequent in bromocriptine-treated patients. 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↗

PubMed1986

Inhibition of noradrenergic neurotransmission by apomorphine and pergolide in the in situ autoperfused rat renal and superior mesenteric vascular beds.

In vitro studies have provided evidence that presynaptic dopamine receptors are present in the rat renal and superior mesenteric vascular beds. To confirm this in vivo, the effects of locally administered apomorphine and pergolide were studied in the in situ autoperfused renal and superior mesenteric vascular beds. Local infusion of apomorphine (1 microgram X kg-1 X min-1 for 5 min) or pergolide (1 microgram X kg-1 X min-1 for 5 min) into either the renal or the superior mesenteric artery had no effect on perfusion pressure per se. In the renal vascular bed, the pressure response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) was reduced to 49.8 +/- 4.8% by apomorphine and to 54.8 +/- 2.7% by pergolide; in the mesenteric vascular bed, apomorphine reduced the pressure response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) to 53.8 +/- 2.9, pergolide to 52.0 +/- 1.8%. Increases of perfusion pressure in the renal and in the mesenteric vascular bed induced by locally administered noradrenaline were not modified by apomorphine or pergolide. In both vascular beds, the inhibition of the stimulation-evoked pressure responses by apomorphine or pergolide was completely antagonized by local administration of the dopamine receptor antagonist haloperidol in a dose (1 microgram X kg-1) which did not influence the inhibitory effect of the alpha 2-adrenoceptor agonist UK-14,304; the alpha 2-adrenoceptor antagonist rauwolscine, in a dose (100 micrograms X kg-1) which completely antagonized the inhibitory effect of UK-14,304, did not antagonize the inhibitory effects of apomorphine and pergolide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Evidence that apomorphine and pergolide induce rotation in rats by different actions on D1 and D2 receptor sites.

Apomorphine and the ergot derivative pergolide induced dose-dependent contralateral rotation in rats with unilateral 6-hydroxydopamine denervation of the ascending dopamine pathways. This was interpreted as an action on supersensitive receptors. However, large differences were found when comparing apomorphine and pergolide dose-response curves as well as the patterns of rotational behaviour the compounds elicited. Pergolide had a steep dose-response curve, while apomorphine had a flatter curve reaching a plateau at the dose of 1 mg/kg s.c. In doses higher than 1 mg/kg, apomorphine induced self-mutilation, while this was infrequent after pergolide. Apomorphine induced a two-peak pattern of rotation that never occurred when the same rats were tested with the ergot derivative. Both drugs induced dose-dependent ipsilateral rotation in animals with unilateral striatal kainic acid lesions but at doses 100 times higher. This effect was interpreted as an action on normosensitive receptors situated on the intact side. The differences between apomorphine and pergolide may be explained in terms of actions on different dopamine receptors, since the agonists were differently inhibited by neuroleptics acting on D1- or D2-type receptors. The D1/D2 antagonist cis-flupenthixol blocked both apomorphine and pergolide with similar potency, while sulpiride, a substituted benzamide devoid of any effect on D1 receptors, was a poor inhibitor of the apomorphine response. In contrast, sulpiride blocked pergolide rotation at doses 1000 times lower than those needed to block apomorphine rotation. Our results suggest the existence of functionally distinct sites related to the D1/D2 receptor classification.

Animals↗

PubMed1988

Treatment of Parkinson's disease with pergolide: a double-blind study.

Pergolide is a potent dopamine agonist and is known to have anti-Parkinson properties. We administered pergolide to patients with suboptimal control of Parkinson's disease who had a short-duration response to carbidopa-levodopa in a 6-month, double-blind study. Pergolide added to the carbidopa-levodopa regimen resulted in both subjective and objective improvement in comparison with placebo. In patients who tolerated pergolide, the median time spent in the "off" (parkinsonian) state was reduced from 5.0 to 2.2 hours daily (compared with a 0.3-hour reduction in the placebo group). These patients were able to decrease the median frequency of carbidopa-levodopa dosage from 7.5 to 5.0 doses daily (no change in the placebo group). Prolongation of the "on" response (optimal response to treatment) to single doses of drugs was corroborated by monitoring of the patients' Parkinson response cycle. The peak response was also improved in most patients. Of 25 patients randomized to the pergolide group, 7 were unable to tolerate this drug; confusion or hallucinations occurred in 4 of these patients, and chest pain, leukopenia, and nonspecific dizziness, respectively, developed in the other 3. All adverse events were reversible with reduction of the dose or discontinuation of the pergolide regimen. In conclusion, patients with Parkinson's disease who experience clinical fluctuations with carbidopa-levodopa may be helped by the addition of pergolide to the therapeutic regimen.

Activities of Daily Living↗

PubMed1981

Physiologic disposition of pergolide.

Pergolide, a synthetic ergoline, is a potent long-acting dopaminergic drug effective in Parkinson's disease and amenorrhea-galactorrhea. After 138 micrograms 14C-pergolide orally to healthy subjects, radioactivity was present in plasma and red blood cells. Salivary radioactivity was one third to one tenth that in plasma. Radioactivity in plasma appeared after 15 to 30 min, peaked at 1 to 2 hr, and was barely detectable after 96 hr. Plasma radioactivity was not attributable to pergolide, and the levels did not correlate well with the duration of the prolactin-lowering effect induced by pergolide. Pergolide became bound to several plasma proteins and could not be displaced by other drugs that are also bound or by possible metabolites of pergolide. Radioactivity was eliminated as pergolide metabolites in urine (55%), feces (40%), and breath (5%, as 14CO2).

Adult↗

PubMed2002

The effect of pergolide on cognitive performance of young and middle-aged rats.

In this study, we investigated the effect of pergolide, a dopaminergic agonist, on cognitive ability in young and middle-aged rats using the Morris Water Maze (MWM). Pergolide 0.5/mg/day i.p. was administered to young and middle-aged rats, whereas only vehicle was given to their age-matched controls. During the acquisition period of 6 days, young rats showed normal escape latency pattern, which was not affected by pergolide. Middle-aged rats, however, showed poor escape latency pattern, and this poor pattern was also not affected by pergolide. On the 7th day, pergolide decreased retention time of young rats compared to control values. Middle-aged rats also showed reduced retention time. In contrast to the findings of young rats, retention time was not affected by pergolide in middle-aged rats. We concluded that pergolide does not alter escape latency at any age. It has a negative effect on retention time of young rats, whereas it has no effect on middle-aged ones.

Aging↗

PubMed2002

Effects of pergolide on blood pressure and tissue injury in DOCA-salt hypertension.

The present study was designed to evaluate the possible antioxidant effect of pergolide, a DA-2 receptor agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in endogenous endothelin-1 (ET- 1) production and organ hypertrophy. Male Sprague-Dawley rats were uninephrectomized (UNx) or uninephrectomized, and received subcutaneous implants of DOCA and drank 1% sodium chloride (DOCA). DOCA rats were treated daily for 3 weeks with pergolide (1 mg/kg, i.p.) or vitamin C (1 mg/rat, orally). DOCA-salt treatment increased systolic blood pressure (SBP) in UNx rats by 45 +/- 2 mmHg from 117 +/- 5 to 162 +/- 10 mmHg (p < 0.05), an effect blunted by pergolide and vitamin C. Superoxide generation was not increased in DOCA rats; however, both pergolide and vitamin C significantly reduced superoxide generation by 49 +/- 7% and 52 +/- 13%, respectively (p < 0.05). Plasma ET-1 levels increased twofold in UNx rats but was reduced to 42 +/- 7% (p < 0.05) in DOCA compared to UNx rats. Pergolide and vitamin C reduced plasma ET-1 levels further by 43 +/-10% (p < 0.05) and 46 +/- 8% (p < 0.05), respectively. Pergolide increased urinary Na+ excretion but did not alter urinary protein excretion or the left ventricular and aortic hypertrophy in DOCA rats. These data suggest that the reduction of SBP by pergolide in DOCA-salt hypertension may be attributed to its natriuretic ability, not its ability to reduce superoxide generation or ET- 1 production.

Animals↗

PubMed1980

Pergolide mesylate: a potent day-long inhibitor of prolactin in rhesus monkeys and patients with Parkinson's disease.

The effect of a new synthetic ergot alkaloid, pergolide mesylate, on the inhibition of PRL during 24-h periods was evaluated in four rhesus monkeys and three patients with Parkinson's disease. In the monkeys, the mean PRL level during the 24-h period fell to 24% of control in response to 50 micrograms. With 1000 micrograms pergolide daily and to 6.6% of control with 200 micrograms pergolide daily, PRL was unmeasurable in the great majority of samples over 24 h. In addition, the marked episodic fluctuation in PRL occurring in controls was not observed in treated animals. In three patients with Parkinson's disease, treatment with pergolide also resulted in uniform 24-h suppression of PRL. In one patient on pergolide (100 micrograms/day), the mean 24-h PRL level fell to 18% of control, and in two other patients on 200 and 600 micrograms pergolide, respectively, whose mean PRL levels were 4.1 and 7.4 ng/ml, respectively, before treatment, no PRL was detected in any of the blood samples obtained during the 24-h periods. These data provide evidence that pergolide is a potent inhibitor of PRL in rhesus monkeys and in patients with Parkinson's disease; the effect is iniform over 24-h periods.

Animals↗

PubMed2003

Tic reduction with pergolide in a randomized controlled trial in children.

OBJECTIVE: To determine whether pergolide, a mixed D1/D2/D3 dopamine agonist, is efficacious and safe in the treatment of children with chronic tic disorders and Tourette syndrome. BACKGROUND: Neuroleptics, which block dopamine transmission, are currently used to treat children with severe tics, but major side effects and limited efficacy reduce clinical utility. Prior open-label and crossover studies of pergolide suggest potential benefit. METHODS: The authors enrolled 57 children and adolescents, ages 7 to 17 years, randomizing them in a 2:1 ratio to either pergolide (0.15 to 0.45 mg per day) or placebo. Tic symptoms had to be >30 on the Yale Global Tic Severity Scale (YGTSS). The primary outcome measure was change in tic severity assessed by YGTSS. RESULTS: Compared to placebo treatment, pergolide treatment was associated with lower tic severity scores (treatment effect 8.8, pergolide vs placebo; 95% CI 0.1 to 17.6; p = 0.05) and attention-deficit hyperactivity disorder symptoms scores (treatment effect 3.8; 95% CI 0.7 to 6.8; p = 0.02). No patient had a serious adverse event and pergolide was well tolerated. CONCLUSIONS: In this randomized, placebo-controlled trial, pergolide appeared to be an efficacious and safe medication for tic reduction in children, and may also improve attention-deficit hyperactivity disorder symptoms.

Adolescent↗

PubMed1995

Pergolide in the treatment of Parkinson's disease.

Three trials evaluated the efficacy and safety of pergolide. Eighty-six de novo patients and 314 patients already receiving levodopa were enrolled in an open-label study. Of the de novo patients, 47.5% showed a marked or moderate improvement and 32% showed a mild improvement. In the levodopa add-on group, 53.8% showed marked or moderate improvement and 36.3% showed mild improvement. In a short-term, double-blind study, the efficacy of pergolide was compared with that of bromocriptine. One hundred seventy-two patients were randomized to receive pergolide, and 173 were randomized to receive bromocriptine. In de novo patients, bromocriptine (n = 49) and pergolide (n = 49) demonstrated similar efficacy. However, significantly more levodopa-treated patients in the pergolide group, compared with the bromocriptine group, demonstrated marked or moderate improvements in several items of the rating scale score. In a long-term study, 151 of 314 patients receiving pergolide in combination with levodopa remained in the study for 3 years, and 127 for 4 years, and in these patients the initial improvement was maintained. In 18 of 62 de novo patients, the initial improvement was maintained for up to 3 years. These trials indicate that pergolide has efficacy in patients with Parkinson's disease, either as monotherapy or in combination with levodopa.

Double-Blind Method↗

PubMed1982

Effects of pergolide, a dopamine receptor agonist, and clonidine on cardiovascular responses evoked by activation of peripheral sympathetic outflow in rats.

In pentobarbital anesthetized rats, pergolide (10.0 micrograms/kg, i.v.) and clonidine (3.0 micrograms/kg, i.v.) produced similar significant decreases in heart rate and carotid artery pressure. Sulpiride (0.3 mg/kg, i.v.) did not change the effects of clonidine but inhibited entirely the hypotension and partly the bradycardia produced by pergolide. However, yohimbine (0.4 mg/kg) antagonized the cardiovascular effects of clonidine and reduced the bradycardia produced by pergolide. In pithed rats with an experimental, submaximal tachycardia evoked by sustained electrical stimulation of the thoracic sympathetic outflow pergolide and clonidine decreased heart rate. This effect was antagonized by yohimbine (0.1 mg/kg, i.v.) but by not sulpiride (0.3 mg/kg, i.v.). In adrenalectomized, propranolol pretreated pithed rats the pressor responses to 15 sec periods of electrical stimulation of the entire spinal cord were depressed only by pergolide. This effect was blocked by sulpiride. These findings indicate that in the pithed rat the inhibition of neural sympathetic tachycardia by clonidine and pergolide is mediated by stimulation of cardiac presynaptic alpha 2-adrenoceptors. However, only pergolide decreased significantly the pressor responses evoked by electrical stimulation of the peripheral sympathetic outflow and this effect resulted from activation of dopamine receptors located on postganglionic sympathetic neurons innervating resistance blood vessels. Thus, vascular presynaptic alpha 2-adrenoceptors do not appear to contribute to the significant hypotensive effect exerted by 3.0 micrograms/kg, i.v. clonidine in intact rats. Finally, it is suggested that neuronal dopamine receptors might be considered potential target sites for novel peripherally acting antihypertensive agents.

Animals↗