[Clinical comparision of alpha dihydroergocryptine against cabergoline in the treatment of the fibrocystic mastopathy]. / Comparación clínica de alfa dihidroergocriptina contra cabergolina en el tratamiento de la mastopatía fibroquística.

BACKGROUND: Fibrocystic breast disease is one of the most frequent conditions of the breast among women from 30 to 49 years, with a frequency of about 60%, hence the interest in studying and treating it with the most advanced and effective resources. OBJECTIVE: To compare the efficacy and adverse events of alpha dihydroergocryptine with cabergoline in patients with fibrocystic breast disease. MATERIAL AND METHODS: A prospective, longitudinal, open, comparative study between alpha-dihydroergocryptine and cabergoline, made in the service of Gynecology and Obstetrics at the Dr. Miguel Silva General Hospital in Morelia, Michoacán. 171 patients diagnosed with fibrocystic breast disease were randomly assigned to the alpha-dihydroergocryptine or the cabergoline group. Assessments were made at baseline and every month subsequently. The following symptoms were evaluated: breast tenderness, breast pain, lumps and nipple discharge. The concentrations of prolactin were determined and an ultrasound was performed at baseline and at 3 and 6 months, patients were questioned about adverse events. RESULTS: 171 patients were included (81treated with alpha-dihydroergocryptine and 90 with cabergoline); 156 completed the study. The age limits were 18 and 51 years. The evolution time prior to study entry was 17.71 +/- 18.3 months for the alpha-dihydroergocryptine group and 18.57 +/- 20.35 for the cabergoline group. 15 patients discontinued treatment due to adverse events (8 of the alpha-dihydroergocryptine group and 7 of the cabergoline group). The most common adverse event was headache. CONCLUSIONS: In this study alpha-dihydroergocryptine was better tolerated and had better clinical response compared with cabergoline; breast pain and breast tenderness disappeared within the first month of treatment. Adverse events were similar for both treatments.

[Prescription of ergot derivatives for lactation inhibition in France: Current practices]. / Pratiques de prescription des dérivés de l'ergot de seigle dans l'inhibition de la lactation en France.

OBJECTIVES: To provide an overview of ergot derivatives prescription for lactation inhibition in France, either label (bromocriptine 2.5mg and lisuride 0.2mg) or off-label prescription (dihydroergocryptine and cabergoline). PATIENTS AND METHODS: Analysis based on a questionnaire sent to all 618 French maternity wards in 2009, and prescription modalities from social security reimbursement data in the Rhône-Alpes region. RESULTS: The mean response rate to the questionnaire was 43% and main characteristics of respondents in this sample were very close to those found at the national level. The use of bromocriptine (89%) was the most frequently proposed. Dihydroergocryptine and cabergoline were mentioned as first or second alternatives in 39 and 24% of cases, respectively. Lisuride, homeopathy and phytotherapy were very rarely mentioned. The analysis of social security reimbursement data in the Rhône-Alpes region between 2008 and 2009 evidenced an increase in the rate of dihydroergocryptine prescriptions (from 37 to 46%), which were more frequent in women also treated with cardiovascular or psychotropic drugs, while that of bromocriptine decreased. CONCLUSION: This study shows that, in France, the main alternative to bromocriptine for lactation inhibition is the off-label use of dihydroergocryptine followed by cabergoline, which seems to be safer.

The history of ergot of rye (Claviceps purpurea) III: 1940-80.

The period 1940-80 in the history of ergot was dominated by two investigators, Arthur Stoll and Albert Hofmann. There was great excitement when their group isolated from ergot preparations the powerful psychotropic agent lysergic acid diethylamide (LSD). It was thought that this substance would help to find the cause of schizophrenia and other psychotic disorders, but it would prove to be a great disappointment and Hofmann would say later, in private, that he regretted having spent so much time on the compound. By contrast, bromocriptine, derived from ergocriptine, would prove a pivotal substance in our knowledge of dopamine receptors in the central nervous system. It is widely used for the suppression of lactation, the treatment of prolactinomas and the management of Parkinson's disease.

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results.

Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30 microM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine on the basis of molecular mass measurements, determined with a time-of-flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy-metabolites in human plasma by LC-MS/MS after oral dosing of dihydroergotoxine mesylate (27 mg) to a healthy volunteer (male, age 45, height 1.93 m, weight 103 kg). In this preliminary approach, the peaks (C(max)) of dihydroergocornine, dihydroergocryptine and dihydroergocristine were about 0.04 microg/l. The peaks (C(max)) of their hydroxy-metabolites were 0.98, 0.53 and 0.30 microg/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma.

Bioequivalence of a novel high-dose oral formulation of alpha-dihydroergocryptine.

The plasma pharmacokinetics of alpha-dihydroergocryptine (DHEC, CAS 14271-05-7) were investigated in 24 patients with Parkinson disease after the administration of repeated oral doses of 40 mg DHEC twice daily by means of a novel 40 mg DHEC tablet (Almirid 40 mg test T) and an established 20 mg DHEC tablet (Almirid 20 mg - reference R). The trial was conducted according to a randomised, controlled, open, within-subject cross-over design; steady-state was established by means of a stepwise up-titration from 5 to 40 mg b.i.d. from day D01 to D19; investigational treatments (40 mg DHEC b.i.d. by means of formulation R and T) were administered on day D20 and D21 according to a randomised, period-balanced within-subject cross-over; treatment with DHEC was down-titrated in stepwise fashion from day D22 to D34. Morning doses of 2 x 20 mg DHEC (reference) yielded a fast and relatively short lasting peak with a geometric mean Cmax of 2157 pg/mL (CV: 0.978) after a median tmax of 1.00 h. Cmin throughout the first 12 h was on average 189 pg/mL (CV: 0.908). There was a quite distinct diurnal effect: evening doses of 2 x 20 mg DHEC (treatment R), yielded a relatively lower exposure with geometric mean Cmax, Cav- and Cmin-values of 800 pg/mL (CV: 0.870), 389 pg/mL (0.813) and 177 pg/mL (CV: 0.942). In contrast, there was relatively little within-subject distinction between the two formulations: for the day profile after the morning dose, the estimated ratios of the true means (Pr:R) for Cmax Cmin and Cav were 1.18 (90% CI: 0.96 to 1.43 - CVm: 0.394), 0.96 (90% CI: 0.86 to 1.09 - CVm: 0.230) and 1.06 (90% CI: 0.93 to 1.21 - CVm: 0.254); for the night profile after the evening dose, the estimated ratio of the true means (muT:muR) for Cmax, Cmin and Cav were 1.11 (90% CI: 0.91 to 1.35 - CVm: 0.395), 1.07 (90% CI: 0.95 to 1.20 - CVm: 0.232) and 1.07 (90% CI: 0.95 to 1.20 - CVm: 0.220). In view of important medical-ethical constraints not to expose an unreasonably high number of subjects, these findings could be accepted as a sufficient demonstration of bioequivalence.

[Effect of alpha dihydroergocryptine in patients with fibrocystic breast disease]. / Efecto del alfa dihidroergocriptina en pacientes con mastopatía fibroquística.

OBJECTIVE: To evaluate the effectiveness of alpha dihidroergocriptine in patients with fibrocystic mastopathy. PATIENTS AND METHODS: Patients with diagnosis of fibrocystic breast disease were included in a prospective longitudinal blind double, controlled with placebo study. Patients were randomly assigned to one of two treatment groups: of treatment group A: Alpha dihidroergocriptine tablets of 10 mg, group B: Placebo, during 6 months. After to basal evaluation, the patients were revised in a monthly way evaluating the following symptoms and signs: mastalgia, mammary tension, presence of nodules, nipple secretion, and the presence of adverse events. RESULTS: 39 patients with alpha dihidroergocriptine and 38 with placebo. Mastodinia, a satisfactory response was observed in 100% of alpha dihidroergocriptine group vs 61.11% of placebo group (p = 0.0002). Mastalgia responded in 100% of alpha dihidroergocriptine group vs 64.86% of placebo group (p = 0.0003). Galactorrea responded 100% of alpha dihidroergocriptine group vs 93.33% of the placebo. The nodules in the group alpha dihidroergocriptine disappeared in 23.1% and in 21.1% of the placebo group. Ultrasound evaluation of the nodules did not show significant differences between both groups. Prolactin levels showed a decrease in the group treated with alpha dihidroergocriptine with an important difference between both groups at the end of the 6 months study period. There were not differences in the presence of adverse events between groups. CONCLUSIONS: Alpha dihidroergocriptine is effective in the treatment of fribrocystic breast disease with minimum adverse events when compared with similar drugs.

Synergistic effect of alpha-dihydroergocryptine and L-dopa or dopamine on dopaminergic neurons in primary culture.

There is an ongoing controversy about potential toxicity of L-3,4-dihydroxyphenylalanine (L-dopa) to dopaminergic neurons in Parkinson's disease (PD). Neuroimaging data suggest that L-dopa accelerates the loss of dopamine nerve terminals, especially at higher doses. The disputed aspect of toxicity and the frequently observed motor complications accompanying L-dopa therapy have led to an increased use of dopamine agonists during the past two decades. Reports describing their neuroprotective potential to dopaminergic neurons have attracted much attention. Here, we describe the novel finding that the combination of a dopamine (DA) agonist, alpha-dihydroergocryptine (DHEC), with L-dopa or DA exerts a synergistic stimulatory effect on dopaminergic neurons in primary culture, while each substance alone had no or less effect. DA receptor stimulation plays a decisive role. The synergistic effect suggests that a combinatory therapy can be beneficial to slow the degeneration of dopaminergic neurons.

Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.

The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001-January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non-Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Non- efficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner.

Alpha-dihydroergocryptine in the long-term therapy of Parkinson's disease.

The trial was designed as an open-label, post-authorisation safety study, aimed to complete the available information on adverse events and drug reactions to alpha-dihydroergocryptine (CAS 14271-05-7, alpha-DHEC). The study included 294 patients with idiopathic Parkinson's disease who received levodopa (CAS 59-92-7, L-DOPA) and started taking alpha-DHEC (Cripar). Adverse events were analysed descriptively, Parkinson's disease symptoms were documented using a questionnaire applied by the physicians. Patients were evaluated at study start and three and six months later, respectively. In 31 patients, 32 adverse events were observed, gastrointestinal and nervous system disorders being the most frequent. Dyskinesias, psychoses/hallucinations, sleep disturbances, and cardiovascular disorders were uncommon (< or = 1%). in total, 21 adverse events were classified as adverse drug reactions. In nearly 80 % of the cases, Parkinson symptoms had improved or completely vanished. Symptoms were unchanged in 16.7 % of patients and had worsened in 3.1%. The results confirm that the use of alpha-DHEC in combination therapy with levodopa in patients with Parkinson's disease is a well-tolerated and efficacious treatment option.

Comparison of alpha-dihydroergocryptine and levodopa monotherapy in Parkinson's disease: assessment of changes in DAT binding with [123I]IPT SPECT.

Putative neurotoxic actions of levodopa and neuroprotective effects of dopamine agonists, as indicated by laboratory and animal studies, provide the rationale to study their effect on the progression of Parkinson's disease. Aim of this pilot study was to compare the effects of monotherapy with the dopamine agonist alpha-dihydroergocryptine (DEC) versus monotherapy with levodopa on nigrostriatal dopaminergic neurons as measured with dopamine transporter (DAT) SPECT. 25 PD patients (H&Y stages 1 to 2.5) entered this study and were treated in a randomized fashion either with DEC (101+/-39 mg) or levodopa (369+/-51 mg) monotherapy. 16/25 patients (8 per group) terminated the study after 52 weeks. In each patient SPECT investigations with [123I]IPT were performed at baseline and after 52 weeks to assess changes of specific DAT binding over time. Changes in clinical symptoms were assessed by UPDRS score. The mean annual decline rate in striatal IPT-binding was lower in the DEC group (8.4%) compared to the levodopa group (10.4%). The difference was most accentuated in the putamen (DEC: 7.3%; levodopa: 16.2%; p = 0.16). Due to the small sample size and the relatively short observation period, however, group differences did not reach a statistical significant level. The results of this pilot study suggest that as compared to levodopa monotherapy DEC may have beneficial effects on decline of dopamine transporter binding similar to those recently described for pramipexole.

Determination of dihydroergocryptine in human plasma and urine samples using on-line sample extraction-column-switching reversed-phase liquid chromatography-mass spectrometry.

A rapid and sensitive assay for the determination of dihydroergocryptine (DHEC) in human plasma and urine samples with dihydroergotamine (DHET) as the internal standard was developed. The procedure employs on-line sample preparation using an extraction pre-column and an octadecylsilylsilica (ODS) analytical column. After centrifugation human plasma or urine were injected onto the pre-column, concentrated and extracted, back-flushed onto the analytical column and eluted with a binary methanol--aqueous formic acid gradient. Either determination of DHEC as well of its mono- and dihydroxy-metabolites was performed by measurement of the signal responses from MS detection in the selected reaction monitoring (SRM) mode using the transition of the respective parent ions to the common daughter ion at m/z=270.2 amu. The limit of quantitation (LOQ) for determinations of DHEC in both plasma and urine were 25 pg/ml for injected sample volumes of 400 microl. Proportionality of signal responses versus concentration was accomplished within the range of 25-1000 pg/ml. Recovery of target analyte from plasma was 99%. Mean values of the coefficients of variation (CV) for the target analyte in plasma ranged from 1.7 to 13.8% (within-day) and 5.0 to 9.1% (between-day) and accuracy from 91.7 to 102.6% for the within-day and from 95.8 to 98.8% for the between-day measurements. The corresponding values for determinations in urine were 1.7-14.5% (within-day) and 5.3-11.8% (between-day) for CV and 95.8-110.7% (within-day) and 100.1-104.6% (between-day) for accuracy.

Influence of lipid lowering fibrates on P-glycoprotein activity in vitro.

Statin/fibrate combinations are frequently used to treat mixed dyslipidemia. However, these combinations may cause life-threatening drug interactions (e.g. rhabdomyolysis) possibly induced by modifications of cytochrome P450 isozyme activities. Some statins are also transported by P-glycoprotein (Pgp) and may act as inhibitors of this drug efflux pump. So far, nothing is known about possible Pgp modulating effects of fibrates. We tested whether gemfibrozil, fenofibrate, fenofibric acid, and bezafibrate inhibit Pgp in vitro using a calcein acetoxymethylester (calcein-AM) uptake assay and confocal laser scanning microscopy with bodipy-verapamil as substrate in L-MDR1 cells, which overexpress human Pgp. In uptake assays in cells with (L-MDR1) and without (LLC-PK1) human Pgp we also investigated whether these compounds are transported by Pgp. Intracellular concentrations were measured by liquid chromatography tandem mass spectrometry. Of the tested fibrates, only fenofibrate increased calcein-AM uptake into cells indicating an inhibition of Pgp mediated transport by this compound. The potency of fenofibrate (mean+/-SD: 7.1+/-3.2 microM), evaluated by calculating the concentration needed to double baseline fluorescence (f2), was similar to that of simvastatin (5.8+/-1.5 microM), lovastatin (10.1+/-1.0), and verapamil (4.7+/-0.8 microM). For simvastatin and fenofibrate Pgp inhibition was confirmed with confocal laser scanning microscopy. Fenofibrate, fenofibric acid, gemfibrozil, and bezafibrate showed no difference in the cellular uptake between LLC-PK1 and L-MDR1, indicating that the tested fibrates are not Pgp substrates. In conclusion, this study demonstrates that fenofibrate inhibits Pgp in vitro with a potency similar to simvastatin.

Single dose pharmacokinetics of alpha-dihydroergocryptine in patients with moderate to severe renal insufficiency.

AIM: This study was carried out to evaluate the pharmacokinetic profile of alpha-dihydroergocryptine (CAS 14271-05-7, DHEC, Almirid) in plasma and urine in patients with moderately to severely impaired renal function (creatinine clearance < 30 ml.min-1.1.73 m-2), following administration of single oral doses. METHODS: This was an open, nonrandomized trial. Seven patients with chronic renal disease and six healthy subjects received a single dose of 20 mg DHEC. Blood and urine samples were taken at specified intervals up to 72 h after dosing. Concentrations of unchanged DHEC were determined by radio-immunoassay (RIA) and concentrations of unchanged DHEC plus pooled metabolites by enzyme-immunoassay (EIA), respectively. RESULTS: In patients with impaired renal function, the mean Cmax and AUC(0-infinity) values for unchanged DHEC were 2.1 (95% confidence interval CI: 0.99 to 4.42) and 1.85 (95% CI: 0.72 to 4.77) times larger than in controls. The 24-h urinary excretion was only 0.3 (95% CI: 0.12 to 0.71) times that in healthy subjects. Similar findings were recorded for total DHEC plus metabolites. CONCLUSIONS: As treatment with DHEC is in general uptitrated starting with doses as low as 5 mg DHEC, which are then increased while accounting for individual effects both in terms of efficacy and tolerability, the observed range of effects of impaired renal function on DHEC's pharmacokinetics does not suggest the need to revise this policy, although lower end-doses are likely to be achieved.

Dihydroergocriptine in Parkinson's disease: clinical efficacy and comparison with other dopamine agonists.

The present paper reviews clinical studies on the use of dihydroergocriptine (DHEC), an ergot derivative with dopamine agonist activity, for the treatment of Parkinson's disease. This compound is a hydrogenated ergot derivative structurally quite similar to bromocriptine, from which it differs because of the hydrogenation in C9 C10 and the lack of bromine in C2. DHEC has a potent D2-like receptor agonist and a partial D1-like receptor agonist activity; because of this biochemical profile, it has been suggested that DHEC may produce fewer side-effects and have clinical efficacy equal to that of a classical dopamine agonist. Several open-label and double-blind studies indicate that DHEC is an efficacious remedy for parkinsonian signs and symptoms. Further studies are necessary to compare DHEC to new dopamine agonists (pergolide, cabergoline, ropinirole, and pramipexole) which have been more recently marketed.

Interaction of cytochrome P450 3A inhibitors with P-glycoprotein.

Many clinically important drug interactions occur due to inhibition of human liver cytochrome P450 3A (CYP3A) metabolism. The drug efflux pump P-glycoprotein (Pgp) can be an additional locus contributing to these drug interactions because there is overlap in drugs that are substrates for both proteins. We screened a number of CYP3A inhibitors (macrolide antibiotics, azole antifungals, and ergotpeptides) for their ability to interact with Pgp, compared with prototypical Pgp inhibitors. We used cell lines expressing human, mouse, and rat mdr1 genes. Pgp antagonism was defined by interactions of the drugs with four cell lines (LLC-PK1, L-MDR1, L-mdr1a, and L-mdr1b) using a microfluorometric calcein-AM assay and characterized for their inhibitor constant (K(i)) toward calcein-AM. The compounds were further defined for their ability to inhibit MDR1 by their effect on vinblastine accumulation into L-MDR1 cells. Representative compounds from each class of drugs were further tested as Pgp substrates, defined by the ability of human Pgp or mouse mdr1a/Pgp to transport them across a polarized kidney epithelial cell in vitro. These same compounds were administered radiolabeled in vivo to mdr1a (+/+) and (-/-) mice and the distribution of radioactivity compared. The results are summarized as follows: 1) Some drug interactions with Pgp were substrate- and/or assay-dependent. 2) Ergot alkaloids were identified as a class of MDR1/Pgp chemosensitizers. 3) The Ergot alkaloids revealed species differences in the structure-activity relationships for inhibition of Pgp. Simultaneous inhibition of Pgp by many CYP3A inhibitors contributes to human variation in the extent of drug-drug interactions.

Behavioral and neurochemical effects of dopaminergic drugs in models of brain injury.

The dopaminergic drugs, ropinirole and dihydroergocryptine (DHECP) were injected subcutaneously (s.c.) at doses of 0.5 and 1 mg/kg/day for 7 days into male rats of the Sprague-Dawley strain. The drug pretreatment reverted amnesia induced in rats by hypobaric hypopxia and tested in active and passive avoidance tasks. Furthermore, a partial restoration of memory retention was found in animals with a 2-month brain occlusive ischemia induced by manipulation of the four major arteries of the brain. No major changes were found in spontaneous motor activity, but drug treatment increased ambulation of animals subjected to acute or chronic experimental manipulation. In a model of kainate-induced epilepsy, ropinirole or DHECP did not affect seizure parameters, but reduced mortality rate. At the end of behavioral procedures, in all animals subjected to hypobaric hypoxia or to brain occlusive ischemia glutathione redox index (glutathione reduced/glutathione oxidized ratio) was measured in the frontal cortex, striatum and hippocampus. It was found that experimental models of brain injury were followed by a decrease of reduced glutathione content in all brain areas. The glutathione redox index was augmented by ropinirole or DHECP treatment in all brain areas. These behavioral and neurochemical findings suggest that ropinirole and DHECP may exert either protective activity (as found in animals pretreated with these drugs and exposed to hypobaric hypoxia) or reversal of brain injury (as found in animals treated after two-month occlusive brain ischemia). Thus, both drugs may be studied as therapeutic agents in brain injuries of various origin.

Influence of the dopamine agonist alpha-dihydroergocryptine on the pharmacokinetics of levodopa in patients with Parkinson's disease.

This study investigated whether chronic coadministration of alpha-dihydroergocryptine (DHEC) altered the plasma pharmacokinetics of individualized treatments with levodopa in 12 patients with Parkinson's disease. Steady-state pharmacokinetics of plasma levodopa (L-Dopa) under combined treatment were compared with those under treatment with L-Dopa alone. There was no evidence of increased exposure to L-Dopa caused by concomitant treatment with DHEC. In contrast, additional treatment with DHEC reduced the overall exposure to L-Dopa (17.5% reduction in area under the curve; 95% CI: 23%-6%). This effect was small but statistically significant for the area under the plasma concentration-time curve, whereas tmax (time of maximum plasma concentration) and peak-to-trough fluctuation were not affected. Cmax (maximum plasma concentration), on average, was reduced to a similar extent (-14.5%; 95% CI: 38% to -17%), albeit not significantly. The magnitude of the interaction does not suggest changing the current clinical practice of up-titrating DHEC and subsequently adapting L-Dopa to the individual needs of patients.

[Neuroprotective effect of alpha-dihydroergocryptine depends on activation of nuclear factor kappa B].

AIM: To investigate the relationship between the neuroprotective effect of alpha-dihydroergocryptine (alpha-DHEC) and the activation of nuclear factor Kappa B (NF-Kappa B). METHODS: Adult male rats were subjected to cerebral ischemia induced by middle cerebral artery occlusion (MCAO). DNA binding activity of NF-Kappa B was determined with electrophoretic mobility shift assay (EMSA) in animals subjected to varying durations of cerebral ischemia. Neuroapoptosis induced by ischemic damage was measured by deoxynucleotidy transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry (FCM) analysis. RESULTS: No change was observed in nuclear NF-Kappa B DNA binding in normal animal. A low level of constitutive NF-Kappa B DNA binding was detected in animals subjected to cerebral ischemia of 1 h, and significant increase in the amount of active NF-Kappa B in nuclear extracts was observed after cerebral ischemia of 3 h, 6 h, and 12 h. Peak of NF-Kappa B DNA binding was observed at the time point of 3 h. Animals subjected to cerebral ischemia of 3 h potentially initiates neuroapoptosis and activates NF-Kappa B in nuclear extract. Alpha-DHEC (100 micrograms.kg-1 and 150 micrograms.kg-1) showed significant protective effect on neuroapoptosis-induced by cerebral ischemia of 3 h, and inhibiting NF-Kappa B activation using 100 mg.kg-1 pyrrolidinedithiocarbamate (PDTC) in the continuous presence of alpha-DHEC, the neuroprotective effect of alpha-DHEC was blocked. CONCLUSION: The findings suggest that the neuroprotetive effect of alpha-DHEC may depend on the activation of NF-Kappa B.

Dihydroergocryptine in the Treatment of Parkinson's Disease / 대한정신약물학회지

OBJECTIVE: This study was performed to investigate the safety and clinical efficacy of Dihydroergocryptine (DHE) in Parkinson's disease. METHOD: Study subjects were 30 patients with idiopathic Parkinson's disease. DHE was administered orally for 3 months. Parkinsonian severity was assessed by UPDRS, UPDRS-motor score, modified Columbia Rating Scale and the number of finger tapping in both hands for 20 seconds. Patients were asked to report any side-effects related to DHE. Various laboratory tests as well as EKG were performed to exclude possible side-effects. RESULTS: Eight patients were dropped out during the first month of DHE treatment. Although about half of the patients experienced dizziness, indigestion and nausea, most of them were mild and transient. Laboratory tests showed mild and reversible increase in liver enzyme level in 4 patients. Three-month DHE therapy significantly reduced parkinsonian severity that 32%, 44%, 52% reduction of UPDRS, UPDRS-motor and MCRS was observed respectively. CONCLUSION: These results suggest that DHE is a safe and effective dopamine agonist and can be used in treatment of Parkinson's disease.