ergoline and Bradycardia

Possible pergolide-induced cardiotoxicity has been reported in open trials. Over a 6-month period of observation, we prospectively analyzed ECGs and 24-hour ambulatory ECG in 23 patients with Parkinson's disease who were randomized in a double-blind fashion to pergolide or placebo treatments. Pergolide therapy was associated with a mild and transient bradycardiac effect, but no clinically significant cardiotoxicity.

Topics: Aged; Bradycardia; Clinical Trials as Topic; Double-Blind Method; Electrocardiography; Ergolines; Female; Heart; Heart Rate; Humans; Male; Middle Aged; Monitoring, Physiologic; Parkinson Disease; Pergolide; Prospective Studies

1. In the present study, we investigated how alloxan-induced diabetes affects the ability of 5-hydroxytryptamine (5-HT) to modulate bradycardia induced in vivo by electrical stimulation of the vagus nerve in pithed rats. We also analysed the type and/or subtype of 5-HT receptors involved. 2. Diabetes was induced in male Wistar rats with a single injection of alloxan (150 mg/kg, s.c.). Four weeks later, rats were anaesthetized, pretreated with atenolol and pithed. Electrical stimulation (3, 6 and 9 Hz) of the vagus nerve resulted in frequency dependent decreases in heart rate (HR). 3. In diabetic rats, intravenous bolus administration of high doses of 5-HT (100 and 200 microg/kg) increased the bradycardia induced by vagal electrical stimulation. Similarly, low doses (10 microg/kg) of the 5-HT(1/7) receptor agonist 5-carboxamidotryptamine (5-CT), increased vagally induced bradycardia. However, at high doses (50, 100 and 150 microg/kg), 5-CT reduced the bradycardia. Attenuation of the vagally induced bradycardia evoked by the higher doses of 5-CT was reproduced by L-694,247 (50 microg/kg), a selective agonist for the non-rodent 5-HT(1B) and 5-HT(1D) receptors. Enhancement of the vagally induced bradycardia elicited by low doses of 5-CT was reproduced by the selective 5-HT(1A) receptor agonist 8-hydroxydipropylaminotretalin hydrobromide (8-OH-DPAT; 50 microg/kg). These stimulatory and inhibitory actions on vagal stimulation-induced bradycardia in diabetic rats were also observed after administration of exogenous acetylcholine. 4. Vagally induced bradycardia in diabetic rats was not affected by administration of the selective 5-HT(2) receptor agonist alpha-methyl-5-HT (150 microg/kg), the selective 5-HT(3) receptor agonist 1-phenylbiguanide (150 microg/kg) or the selective 5-HT(1B) receptor agonist CGS-12066B (50 microg/kg). 5. Enhancement of the electrical stimulation-induced bradycardia in diabetic rats caused by 5-CT (10 microg/kg) or 8-OH-DPAT (50 microg/kg) was abolished by the selective 5-HT(2/7) receptor antagonist mesulergine (1 mg/kg) and the selective 5-HT(1A) receptor antagonist WAY-100,635 (100 microg/kg), respectively. Similarly, pretreatment with the non-selective 5-HT(1) receptor antagonist methiothepin (0.1 mg/kg) blocked the inhibitory effect of 5-CT (50 microg/kg) on the bradycardia induced by vagal electrical stimulation in diabetic rats. BRL-15572 (2 microg/kg), a selective 5-HT(1D) receptor antagonist, inhibited the action of L-694,247 (50

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Acetylcholine; Animals; Biphenyl Compounds; Blood Glucose; Bradycardia; Cholinergic Agents; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Electric Stimulation; Ergolines; Heart; Heart Rate; Injections, Intravenous; Male; Methiothepin; Oxadiazoles; Piperazines; Pyridines; Rats; Rats, Wistar; Receptors, Serotonin, 5-HT1; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Tryptamines; Vagus Nerve

The action of dopamine agonists (apomorphine, bromocriptine, pergolide and quinpirole) on the bradycardia induced in vivo by electrical stimulation of the vagus nerves was studied in pithed rats pretreated with atenolol. The dopamine agonists decreased significantly the vagal-induced but not the acetylcholine-induced bradycardia. The first effect was blocked by (S)-sulpiride or domperidone but not by yohimbine, prazosin or SCH 23390. Both effects were antagonized by methylatropine. The data suggest the presence of presynaptic and/or ganglionic dopamine DA2 receptors in the parasympathetic innervation of the rat heart, stimulation of which inhibits the release of acetylcholine.

Topics: Acetylcholine; Animals; Apomorphine; Bradycardia; Bromocriptine; Decerebrate State; Dopamine Agents; Electric Stimulation; Ergolines; Heart; Heart Rate; Male; Pergolide; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Vagus Nerve

Intracerebroventricular administration of serotonin (5-HT) to conscious rats increases mean arterial pressure (MAP) and decreases heart rate. To determine the mechanisms involved, 5-HT (2.5 micrograms) was injected intracerebroventricularly into conscious rats pretreated with various neurotransmitter and hormone antagonists. The selective 5-HT2 antagonist LY 53857 abolished the increase in MAP and the bradycardia elicited by 5-HT. The increase in MAP produced by 5-HT was potentiated by chlorisondamine (a ganglionic antagonist), unaffected by prazosin (an alpha 1-antagonist) or a vasopressin V1 antagonist alone, but eliminated by the combined pretreatment with prazosin plus the vasopressin antagonist. In contrast, the bradycardia was eliminated by either the vasopressin V1 antagonist or chlorisondamine. In conclusion, 5-HT injected into the lateral cerebral ventricle of conscious rats induces sympathoexcitation and the release of vasopressin, which results in an increase in MAP; 5-HT also elicits a bradycardia mediated through an interaction of the autonomic nervous system with circulating vasopressin.

Topics: Animals; Autonomic Nervous System; Blood Pressure; Bradycardia; Chlorisondamine; Ergolines; Heart Rate; Hypertension; Injections, Intraventricular; Male; Prazosin; Rats; Rats, Inbred Strains; Serotonin; Serotonin Antagonists; Vasopressins