dihydroergotoxine and Parkinson-Disease

In the last 20 years dopamine agonists have been considered more and more helpful as primary therapy for Parkinson's disease (PD). Recently the neuroprotective activity and the therapeutic efficacy of a new ergot derivative, alpha-dihydroergocryptine (DHEC), has been highlighted. In the present work we resume the experimental and clinical data reported about this drug. The rationale for dopamine (DA) agonists as primary therapy for Parkinson's disease (PD) is based on the possibility to delay the onset of long term I-dopa syndrome (LTS) (King, 1992); moreover DA agonists seem to exert a neuroprotective effect on substantia nigra neurons. In fact, they stimulate DA receptors bypassing the degenerating nigrostriatal neurons and their metabolic machinery (Lieberman, 1992; Olanow, 1992); more recently, some studies have shown that these drugs have a direct protective effect too (Felten et al., 1992; Yoshikawa et al., 1994). In this minireview we resume the data reported about neuroprotective activity and therapeutic efficacy of a new ergot derivative, alpha-dihydroergocryptine (DHEC).

Topics: Antiparkinson Agents; Cross-Over Studies; Dihydroergotoxine; Dopamine Agonists; Humans; Neuroprotective Agents; Parkinson Disease; Randomized Controlled Trials as Topic

Topics: Animals; Brain Diseases; Bromocriptine; Dihydroergotamine; Dihydroergotoxine; Dopamine Antagonists; Ergot Alkaloids; Ergotamine; Female; Humans; Methysergide; Migraine Disorders; Parkinson Disease; Pituitary Gland; Prolactin; Receptors, Adrenergic; Receptors, Dopamine; Uterus; Vasoconstriction

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 alpha-dihydroergocryptine (alpha-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.. Thirty-two patients (18 males, 14 females with a mean age of 64.5+/-1.5 SEM) were randomized to alpha-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 alpha-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.. 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 alpha-dihydroergocryptine and 24/36 (67%) for lisuride (P < 0.05).. 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.

Topics: Aged; Antiparkinson Agents; Dihydroergotoxine; Disabled Persons; Dopamine Agonists; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Levodopa; Lisuride; Male; Middle Aged; Movement Disorders; Parkinson Disease; Treatment Outcome

The short-term efficacy of dihydro-alpha-ergocryptine (DEK), a hydrogenate ergot derivative with dopamine (DA) agonist properties was evaluated in 20 L-dopa (LD) stable responder parkinsonian patients by a 6-month double-blind randomized, placebo-controlled study. A motor improvement was found only in DEK-treated patients at mean daily doses of approximately 40 mg, ranging from 15 to 60 mg. The side effects never required the withdrawal of the drug or changes in its schedule. The authors demonstrate the efficacy and the good tolerability of DEK as a new DA agonist drug that can be added to LD in the treatment of parkinsonian patients.

Topics: Dihydroergotoxine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Motor Activity; Parkinson Disease; Synapses; Time Factors

The paper presents the results of administration of alpha-dihydroergocryptine preparation (vasobral) to parkinsonic patients. It was prescribed to 20 patients with parkinsonism together with the specific therapy. Clinical state as well as the level of anxiety and depression was estimated using standard scales both before and after treatment. A high efficiency of vasobral was found as regards such symptoms as disorders of memory, headache, vertigo, a noise in ears and head, asthenic state. In some patients functional activity increased, in 4 patients a dose of dopaminergic preparations was successfully decreased by 25%. An important aspect of vasobral activity was also a decrease of anxious-depressive symptoms. A conclusion was made about efficiency of vasobral in combined treatment of parkinsonic patients.

Topics: Antiparkinson Agents; Caffeine; Dihydroergotoxine; Drug Combinations; Female; Humans; Male; Memory; Middle Aged; Parkinson Disease; Psychomotor Performance; Treatment Outcome

Topics: Dihydroergotoxine; Dopamine Agonists; Humans; Parkinson Disease

Topics: Blood Platelets; Cyclic AMP; Dihydroergotoxine; Humans; Hypertension; Hypotension, Orthostatic; Mood Disorders; Nervous System Diseases; Parkinson Disease; Platelet Aggregation; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Schizophrenia

A low frequency stimulation of the head of the caudate nucleus in freely moving cats leads to an arrest of reactions with an increased muscular tone and tremor. This reaction may serve as an experimental model of one of the expressions of parkinsonism, inasmuch as its accomplishment depends upon the central dopaminergic mechanisms (confirmed on experiments with disulfiram and alpha-methyltyrosine). The similarity is also supplemented by the fact that the arrested reaction is weakened by antiparkinson drugs (d, 1-amphetamine, DOPA, artane) and is increased by neuroeptical preparation (aminazine, haloperidol, reserpine).

Topics: Amphetamine; Animals; Catecholamines; Cats; Caudate Nucleus; Chlorpromazine; Dihydroergotoxine; Disease Models, Animal; Disulfiram; Electric Stimulation; Methyltyrosines; Motor Activity; Muscles; Parkinson Disease; Propranolol