Dihydroergotoxine mesylate for the treatment of sialorrhea in Parkinson's disease.

BACKGROUND: Many patients with Parkinson's disease (PD) suffer from sialorrhea. Sialorrhea is often treated with anticholinergics and botulinum toxin, but some adverse effects have limited the use of these treatments. Dihydroergotoxine mesylate is an α-adrenergic blocking agents as well as some affinities to the dopaminergic and serotonin (5-HT) receptors. In the current study, we examine the safety and efficacy of dihydroergotoxine mesylate in PD patients. METHODS: This study consisted of 2 phases. The intervention was 2.5-mg oral dihydroergotoxine mesylate twice daily in both phases. The first phase is a three-week open-label single-arm trial (n = 10). The second phase was a six-week randomized controlled trials with a crossover design (n = 20). Efficacy was assessed using the United Parkinson's Disease Rating Scale (UPDRS) sialorrhrea subscore and Sialorrhea Clinical Scale for PD (SCS-PD). RESULTS: In the first phase, the UPDRS sialorrhea score was 3.5 ±â€¯0.53 vs. 1.9 ±â€¯0.57 prior to and after the treatment (P = 0.004). The SCS-PD score decreased from 15.8 ±â€¯2.78 to 9.9 ±â€¯3.00 after the treatment (P = 0.005). The response rate (defined by at least 30% reduction in SCS-PD score) was 60%. In the second phase of crossover trial, the UPDRS sialorrhea score was 3.00 ±â€¯0.56 in placebo weeks vs. 2.00 ±â€¯0.65 on dihydroergotoxine in dihydroergotoxine weeks (P = 0.001). The SCS-PD was 12.50 ±â€¯2.84 and 9.25 ±â€¯2.86 versus, respectively (P < 0.001). The response rate was 10% and 55%, respectively (P = 0.003). There were no significant adverse effects. CONCLUSIONS: Dihydroergotoxine mesylate is safe and effective for sialorrhea in PD patients.

Preparation of ergoloid mesylate submicron emulsions for enhancing nasal absorption and reducing nasal ciliotoxicity.

The aim of this investigation was to prepare ergoloid mesylate submicron emulsions (EMSEs) for enhancing nasal absorption of drug and reducing nasal ciliotoxicity. Following intranasal administrations of EMSE and ergoloid mesylate solution (EMS) and intravenous administration of EMS to rats separately at the dose of 2 mg kg(-1), the levels of EM in blood and the cerebrospinal fluid (CSF) were evaluated by microdialysis method. The nasal ciliotoxicity was evaluated by using in situ toad palate model. The absolute bioavailability and the AUC in the CSF following intranasal administration of EMSE (56.3 +/- 5.3%, AUC(CSF) 28,594 +/- 5680 ng ml(-1) min) were statistically higher than those after intranasal administration of EMS (47.4 +/- 3.5%, AUC(CSF) 19,870 +/- 2247 ng ml(-1) min). No significant difference was found for the value of the brain drug direct transport percentage (DTP%) or the drug targeting efficiency (DTE) between the group receiving EMSE and the group receiving EMS. In conclusion, EMSE exhibited higher nasal absorption of EM in rats and significantly lower nasal ciliotoxicity whereas no greater brain-targeting efficiency in comparison with EMS.

Evaluation of brain-targeting for the nasal delivery of ergoloid mesylate by the microdialysis method in rats.

The aim of this study was to quantify the nasal delivery of ergoloid mesylate (EM) to the brain by comparing cerebrospinal fluid (CSF) and plasma EM levels after nasal administration at a dose of 4 mg/kg with those after intravenous administration. Following nasal delivery, EM reached a Cmax value (mean+/-SD) in plasma of 348.41+/-19.47 ng/ml and in CSF of 87.35+/-6.37 ng/ml after 107 and 20 min, respectively, while after intravenous injection, EM reached a Cmax value (mean+/-S.D.) in CSF of 54.81+/-4.92 ng/ml at 60 min and the Cmax in plasma was 1255.51+/-133.59 ng/ml. The AUC(CSF)/AUC plasma ratio (0.48+/-0.05) after intranasal delivery differed greatly from the ratio (0.14+/-0.04) observed after intravenous injection (P<0.05). The further analyzed data demonstrated a statistically significant distribution advantage of EM to the brain via the nasal route, and further suggesting that nasal administration can be a promising alternative for EM that undergoes first-pass metabolism following oral administration.

[Pathogenetic basis for using prodectin and teonicol, redergin and aescuzan in complex treatment of chronic gastritis]. / Patogeneticheskie osnovy primeneniia prodektina i teonikola, redergina i éskuzana pri kompleksnom lechenii khronicheskogo gastrita.

The study of the microvessels in bioptates of gastric mucosa and micro haemocirculation in the conjunctiva of 254 patients with chronic gastritis revealed that exacerbation of the gastric process is going on the background of hard terminal bloodstream disorders. They have the generalized character and picture of the typical chronic relapsing trombohaemorrhagic syndrome. The use of Prodectin (250 mg), Teonicolum (150 mg), Redergin (1 tab.) and Aescuzan (25 dr.) 4 times per day during 3 weeks helps to eliminate the microcirculatory disorders and exacerbation of the chronic gastritis.

Topical vasoactive cream in the treatment of erectile failure: a prospective, randomized placebo-controlled trial.

OBJECTIVE: To repeat a previous study on the use of a topical treatment for erectile failure using a vasoactive cream. PATIENTS AND METHODS: Fourteen patients with erectile failure who had previously responded to intracorporeal injection therapy were enrolled in a randomized placebo-controlled trial. They were given two topical applications, comprising either a cream containing aminophylline, isosorbide dinitrate and co-dergocrine mesylate, or a placebo cream of similar appearance containing no pharmacologically active ingredients. Each patient received 16 applications, eight of the active cream and eight placebo. The creams were applied alternatively on successive occasions and the results recorded. RESULTS: The active cream, applied on 77 occasions, resulted in three good and 13 partial erections. The placebo cream, applied on 76 occasions, yielded four good and 13 partial erections. CONCLUSIONS: We were unable to reproduce the successful results reported by others; in the present study the active cream performed no better than placebo.

Topical treatment of erectile dysfunction: randomised double blind placebo controlled trial of cream containing aminophylline, isosorbide dinitrate, and co-dergocrine mesylate.

OBJECTIVE: To examine the effectiveness in treating impotence to topically applied cream containing three vasodilators--aminophylline, isosorbide dinitrate, and co-dergocrine mesylate--which act by different mechanisms. DESIGN: Randomised double blinded placebo controlled crossover trial over two weeks. SUBJECTS: 36 men with erectile dysfunction randomly allocated to two equal groups. INTERVENTIONS: Active cream containing aminophylline 3%, isosorbide dinitrate 0.25%, and co-dergocrine mesylate 0.05% for one week and placebo for another. MAIN OUTCOME MEASURES: Patients' reported experience of penile responses and side effects of treatment in questionnaires. Penile tumescence and arterial flow in the laboratory. RESULTS: 21 patients reported full erection and satisfactory intercourse with the active cream. Three men reported full erection and satisfactory intercourse with either cream. The active cream was more effective in psychogenic than organic impotence (eight out of nine men with psychogenic impotence achieved a full erection upsilon four out of eight with neurogenic impotence and two out of seven with arterial insufficiency). No major side effects were reported. In the laboratory the active cream increased penile arterial flow (0.19 (SD 0.08) m/s upsilon 0.02 (0.15) m/s with placebo) and induced tumescence in 24 patients. CONCLUSIONS: Topical treatment with a cream containing three different vasodilators might be considered before intracavernous injection of vasoactive agents, particularly in psychogenic impotence.

[Metabolic consequences of long-term antihypertensive treatment with co-dergocrine mesylate/nifedipine in high age groups]. / Metabolische Konsequenzen einer antihypertensiven Langzeitbehandlung mit Co-dergocrinmesilat/Nifedipin im hohen Lebensalter.

Possible metabolic changes during chronic treatment is of specific importance for the development of antihypertensive drugs. The impact of a combination treatment with co-dergocrine mesilate/nifedipine (Pontuc; CAS 8067-24-1 resp. CAS 21829-25-4) on the lipid metabolism as well as hematological and biochemical values was evaluated in a group of hypertensive patients. HDL-cholesterol remained unchanged, whereas total cholesterol and LDL-cholesterol slightly decreased, apoprotein AI increased and apoprotein B decreased. In conclusion the results of this study indicate that co-dergocrine mesilate/nifedipine has no negative impact on the lipid metabolism in patients with essential hypertension.

Clinical pharmacokinetics of the nifedipine/co-dergocrine combination in impaired liver and renal function.

Following a single oral dose of 20 mg nifedipine combined with 2 mg co-dergocrine to 24 subjects, the pharmacokinetics of this drug were studied. 8 normotensive subjects had normal renal and hepatic function, 8 patients had chronic renal insufficiency (creatinine clearance less than 30 ml.min-1) and 8 patients had liver cirrhosis which was confirmed by liver biopsy. The area under the plasma level time curve (AUC infinity) of co-dergocrine increased from 0.59 +/- 0.41 ng.ml-1. (mean +/- SD) in the normals to 1.24 +/- 0.95 ng.ml-1.h in liver cirrhosis (P less than 0.05) and to 1.81 +/- 0.9 ng.ml-1.h in renal failure (P less than 0.05 compared with the control group). Corresponding values for the nifedipine AUC infinity were 564.5 +/- 268 ng.ml-1.h, 1547.5 +/- 1134 (P less than 0.05) and 929 +/- 533 ng.ml-1.h (P less than 0.05; gas chromatographic method). The incidence of adverse effects was lower in patients with renal failure than in subjects with normal renal and liver function as well as in those with liver cirrhosis.

Enhancement of the intestinal absorption of ergot peptide alkaloids in the rat by micellar solutions of polyoxyethylene-24-cholesteryl ether.

The incomplete intestinal absorption of hydrogenated ergot peptide alkaloids as measured in bile duct cannulated rats is much increased when the ergot compounds are administered as micellar solutions together with POE-24-cholesteryl ether. In vitro diffusion experiments with isolated intestinal mucus show that the ergot peptide alkaloids are strongly retained by the mucus layer. It is suggested that the diffusion of the ergot compounds across the mucus barrier is facilitated by micellar entrapment of the drug.

Incorporation, after single and repeated application of radioactive labelled DH-ergot alkaloids in different organs of the cat, with special reference to the brain.

1 h after intravenous administration, 3H-DH-ergot alkaloids showed maximal uptake in the range of 10(-5)M in various visceral organs, and of 10(-7)M in most parts of the CNS of the cat. The clearance function in both groups of tissues was logarithmical linear, the slope of the straight line for the parts of the CNS being considerably flatter. Repeated administration of these drugs demonstrated a higher retention in the CNS than in the other organs. The single-dose level in the CNS is reinforced and, in contrast to liver and lung, maintained for at least 24 h.

[Clinical treatment of peripheral arterial occlusive diseases]. / Zur klinischen Behandlung peripherer arterieller Durchblutungsstörungen

Effectiveness and tolerance of Defluina was studied in a selective open trial including 30 patients (17 males, 13 females, mean age 70 years) suffering from peripheral arterial occlusive diseases of different stages. All patients were treated with Defluina, 20 drops thrice a day during a mean period of 30 days. Simultaneous application of further peripheral vasodilators was excluded. Subjective and objective parameters (pulse, Ratschow's test, walking distance) of 27 patients (15 males, 12 females) were evaluated. After 4 weeks of therapy an improvement of all parameters especially of the walking distance was observed. Within 4 weeks 3 of 5 ulcera cruris as well as an initially existing gangrene were closed. Deflunia was well tolerated by 25 patients, very well tolerated by 2. The therapy was discontinued in 3 patients: 2 because of unchanged complaints after 13 and 20 days of therapy, 1 after 17 days due to dull gastric pain following intake of the drug. Cardiac side-effects or steal phenomena were not observed.