Alpha-dihydroergocryptine in Parkinson's disease: a multiceuntre randomized double blind parallel group study

Abstract

Introduction ‐ A multicentre randomized double‐blind parallel group study was carried out on 68 patients suffering from idiopathic Parkinson's disease (PD) treated with l‐dopa for at least 1 year with inadequate therapeutic responsiveness. The aim of the study was to compare the efficacy of α‐dihydroergocryptine (α‐DHEC) vs lisuride as an adjunct therapy to l‐dopa on dyskinesias and clinical fluctuations (Unified Parkinson's Disease Rating Scale [UPDRS] part IV), on the symptoms pattern (Columbia University Rating Scale [CURS]), on disability (Northwestern University Disability Scale [NUDS]), and to evaluate the incidence of adverse events. Patients and methods ‐ Thirty‐two patients (18 males, 14 females with a mean age of 64.5 ± 1.5 SEM) were randomized to α‐dihydroergocryptine and 36 (16 males, 20 females with a mean age of 61.8 ± 1.4) to lisuride. The treatment lasted 3 months and the dosage was increased until it reached 60 mg/day of α‐dihydroergocryptine and 1.2 mg/day of lisuride, while the l‐dopa dosage was kept constant in both groups. Per protocol and intention to treat analyses were performed on response variables. Results ‐ The adjunctive treatment with the two dopamine agonists determined a significant improvement of PD symptoms in both groups. Alpha‐dihydroergocryptine showed a superior efficacy in reducing the clinical complications (P <0.01 by ANOVA). The number of patients complaining of adverse events was 8 out of 32 (25%) for α‐dihydroergocryptine and 24/36 (67%) for lisuride (P<0.05). Conclusion ‐ Alpha‐dihydroergocryptine effect seems to be superior to that of lisuride both in terms of reduction of l‐dopa therapy long term motor complications (UPDRS part IV) as well as in terms of the incidence and severity of adverse events.

Alpha-dihydroergocryptine in the Long term Therapy of Parkinson’s Disease

“…α-DHEC showed a favourable psychiatric safety profile, with only 1 % of patients presenting psychoses. The result is in agreement with previously reports, that underlined a few cases of hallucination when α-DHEC was administered as an adjunct therapy to levodopa [19], while there was no report of hallucination when the drug was administered as monotherapy even at long term (18-36 months [22, 24]). Also in this case the partial D1 agonistic effect of α-DHEC may give an explanation, as in the development of psychoses and specifically hallucinations mainly the D2 dopamine receptor has been implicated [34,35].…”

“…In comparison to bromocriptine or lisuride, α-DHEC showed favourable results. In a parallel-group study in 68 PD patients already receiving levodopa, α-DHEC (60 mg/day) was significantly superior to lisuride (1.2 mg/ day) in the UPDRS Part IV, the primary efficacy criterion [19]. It was equivalent in the secondary endpoints, which included the CURS and the NUDS (Columbia University Rating Scale and Northwestern University Disability Scale).…”

Alpha-Dihydroergocryptine vs. Pramipexole as Adjunct Symptomatic Treatment of Idiopathic Parkinson’s

“…Ergot derivatives still represent an alternative in the symptomatic treatment of PD, but pergolide and cabergoline cause a heart valve fibrosis in long term treatment, relegating these two drugs to a secondary role in the management of PD [5]. Dihydroergocryptine (DHEC) is a hydrogenated ergot derivative with agonist activity on dopamine D2 receptors, which has been reported as an effective drug in symptomatic monotherapy of PD [4] [6], while there are fewer but promising data [7] on the symptomatic efficacy as an adjunct treatment to levodopa and treatment of motor complications. DHEC has been reported as very safe; no valvular fibrosis, sudden sleep or pathological gambling have ever been reported with this drug, as granted even by EMA [8].…”

Single Dose Pharmacokinetics of α-Dihydroergocryptine in Patients with Moderate to Severe Renal Insufficiency

“…α-Dihydroergocryptine (CAS 14271-05-7, DHEC, Almirid 1) ) is an ergot-derived dopamine agonist for the treatment of Parkinson's disease [1,2]. The substance has agonistic effects at the dopamine D 2 -receptor and, partially, at the dopamine D 1 -receptor [3,4,5].…”