dihydroergotoxine and Cerebrovascular-Disorders

Multi-infarct dementia (MID) characteristically presents with an acute event followed by a stepwise and fluctuating downhill course. Progression is generally considered the consequence of recurrent stroke (Hachinski, 1983): the mainstay of treatment, therefore, is the prevention of further ischemic events.

Topics: Cerebrovascular Disorders; Dementia, Multi-Infarct; Dihydroergotoxine; Humans; Hypertension; Naloxone; Piracetam; Pyrrolidines

While their importance in the market-place is steadily increasing in developed (mainly continental Europe) and even in developing countries, compounds included in the broad category of 'cerebroactive' drugs hardly rate a mention in reference pharmacology and therapeutics textbooks. It is an undeniable fact, however, that the principal users or targets of this drug class, mainly elderly people, represent an increasingly worrying problem, with their often puzzling cohort of ill-definable and even less predictable neurological and mental symptoms. The combination of the above factors cannot but produce a rather confused situation, in which the pressure to treat and the adherence to scientifically rigorous assessment are likely to prevail alternately, on a purely casual basis. This review aims to provide sound methodological guidelines for assessment of 'cerebroactive' drugs in a not always easily accessible literature. It covers firstly the general problems of stroke, dementia and 'common symptoms' of the elderly, and then looks in detail at those compounds which have to date attracted most attention (ergot derivatives, cinnarizine, flunarizine, vincamine, eburnamonine, naftidrofuryl, oxpentifylline, piracetam and citicoline), as well as those which are currently considered investigational (choline and lecithin). The pharmacology and available clinical studies of each drug are examined. No therapeutic indication can be derived from the available evidence, as the few positive results do not go beyond random improvement of symptoms. More fundamentally, the lines of research which need to be pursued most intensively relate to better preliminary definition of diagnostic and prognostic criteria and, with the establishment of adequate testing tools for the assessment of behaviour and neuropsychological performance, those basal conditions which are modified 'naturally' or by drugs.

Topics: Adult; Aged; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Cytidine Diphosphate Choline; Dementia; Dihydroergotoxine; Humans; Middle Aged; Nafronyl; Pentoxifylline; Piracetam; Vasodilator Agents; Vincamine

Topics: Aged; Animals; Betahistine; Cerebrovascular Circulation; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Dementia; Dihydroergotoxine; Humans; Isoxsuprine; Nicotinic Acids; Nylidrin; Rats; Receptors, Adrenergic; Receptors, Histamine; Vasodilator Agents; Vincamine

Topics: Adrenergic alpha-Antagonists; Aminophylline; Angina Pectoris; Bradycardia; Bronchial Diseases; Cerebrovascular Disorders; Coronary Circulation; Coronary Disease; Dementia; Dihydroergotoxine; Ethylamines; Furans; Humans; Hypotension; Injections, Intramuscular; Injections, Intravenous; Moxisylyte; Naphthalenes; Nitrates; Oxprenolol; Phenoxybenzamine; Practolol; Propionates; Propranolol; Vasodilator Agents

Topics: Adult; Aged; Caffeine; Cerebrovascular Disorders; Chronic Disease; Dihydroergotoxine; Drug Combinations; Female; Humans; Male; Middle Aged; Treatment Outcome

Chronic cerebrovascular disturbances of the aged are characterized by a decline of attention. When these patients undergo pharmacological treatment, it is very difficult to distinguish between a direct benefit and/or a secondary effect on memory resulting from attention improvement. In our study we have proposed and evaluated a new method for identifying the different components of therapeutic efficacy on memory and attention in chronic cerebrovascular patients. This method is based on the use of the Randt Memory Test, traditional scores of memory efficiency (Acquisition, Recall, and a combined index), and the RMT three-factor scores derived from a structural model of memory functioning. The three scores have been called Encoding and Organization, Cognitive Efficiency, and Attention Efficiency. Participants were 96 selected chronic cerebrovascular patients treated in a double-blind study for 12 weeks with dihydroergocristine versus placebo. While changes in both acquisition and recall scores were related to the treatment, only changes of the Encoding and Organization factor scores were systematically related to therapy. Changes in Attention Efficiency were positively related to therapy only in proportion to the degree of cerebrovascular impairment.

Topics: Attention; Cerebrovascular Disorders; Chronic Disease; Dihydroergotoxine; Double-Blind Method; Effect Modifier, Epidemiologic; Female; Geriatric Assessment; Humans; Male; Memory; Middle Aged; Models, Neurological; Sensitivity and Specificity

An example of multidimensional assessment procedure applied to the study of treatment effects in a type of pathological aging is presented in this paper. Data discussed here come from a clinical trial performed to evaluate the effects of an ergot derivate, dihydroergocristine, in CCVD memory deficits. The multidimensional assessment procedure consisted of behavioral, clinical, and psychometric measures aimed to identify both the results related to drug activity (experimental validity), and the implications that these eventual drug-induced changes have on the everyday life patients' competence (clinical validity). 97 out-patients (both sexes were represented), with a mean age of 61.21 y (SD 7.29), who suffered from mild to moderate chronic cerebro-vascular disturbances were included in this double-blind study only when they met rigid inclusion criteria. The experimental period was 12 weeks. Results indicate a pattern of convergent, statistically significant, changes which evidence how treatment-associated memory changes are accompanied by an improvement of emotional and physical well being and by a modification of behavioral structure which is characterized by greater efficiency and greater responsiveness to stimuli.

Topics: Aged; Cerebrovascular Disorders; Chronic Disease; Clinical Trials as Topic; Dihydroergotoxine; Double-Blind Method; Female; Humans; Male; Memory Disorders; Mental Processes; Middle Aged; Psychiatric Status Rating Scales

Seventy-six patients took part in a randomized, comparative study of the efficacy of buflomedil hydrochloride and dihydrogenated ergot alkaloids in the treatment of senile dementia associated with cerebrovascular insufficiency. Efficacy was assessed by the patients' performance in four psychometric tests. The results showed that a trend in favour of the buflomedil group in three of the tests became statistically significant in the fourth. Both drugs appeared to be safe, causing no marked adverse reactions. In conclusion, buflomedil is as effective or more effective than dihydrogenated ergot alkaloids in the treatment of senile dementia associated with cerebrovascular insufficiency and could prove a valuable addition to long-term therapy if further studies support the trend shown in this study.

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dementia; Dihydroergotoxine; Female; Humans; Male; Middle Aged; Psychological Tests; Pyrrolidines; Random Allocation; Vasodilator Agents

Topics: Adult; Aged; Aspirin; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Dipyridamole; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation; Sulfinpyrazone

The aim of the trial was to compare the clinical efficacy of dihydroergotoxin with a placebo, and to define its indications in the treatment of acquired dementia of abiotrophic origin (degeneration by primary cerebral atrophy) or arteriopathic (deterioration as the result of multiple cerebral infarcts) origin. It was a single centre, double-blind, randomized, controlled, experimental clinical trial. The trial involved 3 groups, each corresponding to a stage of increasing severity. Each group was randomized separately. The separation between the abiotrophic dementia group and the arteriopathic dementia group was made after the trial, on the basis of clinical criteria (Hachinski ischemic score), and a scan when applicable. The number of subjects necessary was fixed at 100 (33 per group). The duration of the trial was 6 months per patient.

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dementia; Dihydroergotoxine; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Random Allocation; Research Design

Many controlled double-blind clinical trials against placebo and other drugs have clearly demonstrated the activity of dihydroergotoxine mesylate (DHT) on some symptoms of chronic senile cerebral insufficiency (CSCI). In spite of this, there is still some controversy about the usefulness of DHT for treatment of CSCI, as it seems to be hard to transpose the results of these studies to treatment of a population with DHT. Trying to overcome this criticism, a multicenter double-blind, placebo-controlled long-term (1 year) clinical trial has been planned, using very simple criteria for patient selection and easy to use assessment devices. Fifty two centres distributed throughout Italy were invited and 40 took active part in the study. The present report deals with data collected for analysis on Aug. 31, 1982. On this date 559 patients entered the study and 458 were under treatment (229 on DHT 1.5 mg t.i.d. and 229 on placebo). 101 patients dropped out (48 on DHT and 53 on placebo). 388 patients (195 on DHT and 193 on placebo) had completed 6 months and 204 (111 on DHT and 93 on placebo) had completed 1 year of treatment. The data from patients who completed 6 and 12 months of treatment period were analyzed statistically using Student t tests for paired and unpaired data, the large number of patients being adequate protection against any non normality in the distribution of the data. Differences with 2P values of 0.01 or less were considered significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Cerebrovascular Disorders; Chronic Disease; Clinical Trials as Topic; Dihydroergotoxine; Double-Blind Method; Female; Humans; Male; Middle Aged; Placebos; Psychological Tests

Basic pharmacologic evidences have suggested the effects of dihydroergotoxine mesylate (DEM) on neurotransmitters. In its clinical use, however, various therapeutic effects and side effects are observed when the dose is changed, because of the complexity of this compound and the delicate mechanism of neurotransmitters in the brain, especially when modified by aging and vascular lesions. In order to investigate the optimal dose, a double-blind study in 550 patients with cerebrovascular disorders was carried out at 68 centers under observation by experienced specialists. Dihydroergotoxine mesylate in sublingual tablets, 3 mg daily, and in oral tablets, 6 mg daily, respectively, was given for 12 weeks, and therapeutic effects at those doses were compared by a double-blind method. In utility ratings for subjective and psychiatric symptoms, the effects in the oral tablet group at a daily dose of 6 mg were significantly superior to those in sublingual tablet group at a daily dose of 3 mg. There was no significant difference between those two groups in the comparison of side effects. These results show that the daily oral administration of 6 mg of DEM is more suitable for the improvement of subjective and psychiatric symptoms due to cerebrovascular disorders than is the daily sublingual administration of 3 mg. These results suggest that, despite much complexity in the neurohumoral transmitter mechanism in the brain, relatively simple dose-dependent efficacy of the drug in the range of the therapeutic doses was confirmed for many subjective and psychiatric symptoms of patients with cerebrovascular disorders.

Topics: Administration, Oral; Adult; Aged; Central Nervous System Diseases; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Mental Disorders; Middle Aged; Random Allocation

While their importance in the market-place is steadily increasing in developed (mainly continental Europe) and even in developing countries, compounds included in the broad category of 'cerebroactive' drugs hardly rate a mention in reference pharmacology and therapeutics textbooks. It is an undeniable fact, however, that the principal users or targets of this drug class, mainly elderly people, represent an increasingly worrying problem, with their often puzzling cohort of ill-definable and even less predictable neurological and mental symptoms. The combination of the above factors cannot but produce a rather confused situation, in which the pressure to treat and the adherence to scientifically rigorous assessment are likely to prevail alternately, on a purely casual basis. This review aims to provide sound methodological guidelines for assessment of 'cerebroactive' drugs in a not always easily accessible literature. It covers firstly the general problems of stroke, dementia and 'common symptoms' of the elderly, and then looks in detail at those compounds which have to date attracted most attention (ergot derivatives, cinnarizine, flunarizine, vincamine, eburnamonine, naftidrofuryl, oxpentifylline, piracetam and citicoline), as well as those which are currently considered investigational (choline and lecithin). The pharmacology and available clinical studies of each drug are examined. No therapeutic indication can be derived from the available evidence, as the few positive results do not go beyond random improvement of symptoms. More fundamentally, the lines of research which need to be pursued most intensively relate to better preliminary definition of diagnostic and prognostic criteria and, with the establishment of adequate testing tools for the assessment of behaviour and neuropsychological performance, those basal conditions which are modified 'naturally' or by drugs.

Topics: Adult; Aged; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Cytidine Diphosphate Choline; Dementia; Dihydroergotoxine; Humans; Middle Aged; Nafronyl; Pentoxifylline; Piracetam; Vasodilator Agents; Vincamine

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Female; Humans; Male; Mental Disorders; Middle Aged; Nervous System Diseases

Topics: Adult; Blood Pressure; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Drug Combinations; Female; Humans; Intelligence Tests; Male; Middle Aged; Nicotinic Acids; Theobromine; Vasodilator Agents

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Double-Blind Method; Humans

Topics: Aged; Animals; Betahistine; Cerebrovascular Circulation; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Dementia; Dihydroergotoxine; Humans; Isoxsuprine; Nicotinic Acids; Nylidrin; Rats; Receptors, Adrenergic; Receptors, Histamine; Vasodilator Agents; Vincamine

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Drug Evaluation; Humans; Intracranial Arteriosclerosis; Middle Aged

In a controlled double-blind trial in 80 patients with cerebrovascular and cardiac insufficiency the differentiated effect of a combination therapy with cardiac glycosides and Hydergin were studied both with regard to parameters of cerebral organic and cardiac performance. Two randomized collectives of patients with an average age of 63 years were compared with each other for this purpose. They received either acetyldigoxin (0.4 mg/day) alone or in combination with Hydergin (3 mg/day). Duration of treatment was 8 weeks altogether. The single treatment with the cardiac glycoside alone does not lead to a satisfactory improvement in the symptoms of cerebral attacks. The results presented of this study support the necessity in these patients of an internist basic therapy in combination with a preparation like Hydergin acting favorably on cerebral metabolism.

Topics: Acetyldigoxins; Cerebrovascular Disorders; Digoxin; Dihydroergotoxine; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Adult; Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Drug Evaluation; Humans; Intracranial Arteriosclerosis; Middle Aged

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Double-Blind Method; Female; Humans; Male; Middle Aged; Neurocognitive Disorders; Placebos; Tablets

A prospective study over 15 months in 100 elderly patients with signs of cerebro-vascular impairment demonstrated by psychometric testing that Hydergine (an ergot alkaloid preparation: 4.5 mg daily) compensated the signs of dementia, present in the placebo group, and in some patients actually brought about a significant improvement in mental activity. Similar compensatory effect was also demonstrable in cerebral haemodynamics: in the placebo group there was a progressive increase in cerebral circulation time, an expression of decreased cerebral blood flow, while with Hydergine cerebral circulation time was shortened and stabilized. Serial EEGs, obtained in parallel with psychometric and circulation time tests, demonstrated a marked increase in the 8-10 Hz pattern which corresponds to the physiological alpha activity in this age group. Furthermore, there was a diminished variability in performance in the tested frequency bands with Hydergine, the opposite tendency being obtained in the placebo group.

Topics: Aged; Cerebrovascular Circulation; Cerebrovascular Disorders; Dementia; Dihydroergotoxine; Double-Blind Method; Electroencephalography; Humans; Placebos; Prospective Studies; Psychological Tests; Time Factors

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Digoxin; Dihydroergotoxine; Drug Combinations; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Double-Blind Method; Drug Evaluation; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Vascular Diseases

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Drug Tolerance; Emotions; Female; Humans; Ischemia; Male; Mental Processes; Middle Aged; Motor Activity; Piperazines; Piribedil; Vascular Diseases

Topics: Acetyldigitoxins; Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Digitoxin; Dihydroergotoxine; Drug Combinations; Drug Evaluation; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Digoxin; Dihydroergotoxine; Drug Combinations; Female; Humans; Male

The efficacy of Hydergin was compared against placebo in a 15 weeks cross-over trial in 51 patients with cerebral insufficiency. The daily dosage was 3 mg of Hydergin. Criteria of evaluation consisted of clinical rating and electroencephalographic registrations, which were evaluated visually and partly automatically. The clinical symptoms as well as the electroencephalographic criteria (base line activity, theta- and delta activity) were both positively influenced by Hydergin. The base-line activity was stabilised and the alpha activity of the power spectrum increased. The most impressive result was the carryover effect of Hydergin, which could still be demonstrated in the post trial period. In case of "dizziness" the good results were limited to the period of active treatment. The relations between symptomatic and more basic therapy of cerebral insufficiency will be discussed.

Topics: Aged; Brain Chemistry; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Electroencephalography; Female; Humans; Mental Disorders; Neurocognitive Disorders; Placebos; Vertigo

Topics: Age Factors; Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Dihydroergotoxine; Drug Evaluation; Ergoloid Mesylates; Humans; Placebos

A study was based on the survey of 419 neurologists and 1189 their patients with different forms of cerebrovascular diseases using a specially developed questionnaire. In most cases, vasobral was used as a monotherapy or in a complex treatment. Twenty-two percent of physicians reported that vasobral was the most effective compared to other drugs. The good tolerability of treatment (18%) and the broad spectrum of indications and clinical effects (17%) were reported as well. The large percentage (75%) of patients indicated the positive effect of vasobral on memory, reasoning, vertigo etc The maximal effect was identified in the treatment of mild cognitive impairment caused by chronic brain ischemia and vertebrobasilar insufficiency. Vasobral is recommended for a use in a complex therapy in patients with more severe brain lesions and cognitive deficit.

Topics: Caffeine; Cerebrovascular Disorders; Cognition; Cognition Disorders; Dihydroergotoxine; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Memory; Patients; Physicians; Surveys and Questionnaires; Vertigo

Topics: Aged; Brain Ischemia; Cerebrovascular Disorders; Dihydroergotoxine; Female; Humans; Male; Middle Aged; Neurocognitive Disorders

Topics: Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Dihydroergotoxine; Humans; Hypertension; Middle Aged

Topics: Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Dihydroergotoxine; Drug Evaluation; Female; Humans; Hypertension; Male; Middle Aged; Migraine Disorders; Vascular Diseases

Topics: Aged; Cerebrovascular Disorders; Chronic Disease; Dihydroergotoxine; Drug Evaluation; Female; Humans; Male; Middle Aged; Nicotinic Acids; Nimodipine; Vasodilator Agents

The effects of a new eburnamenine derivative (3 beta,14 alpha, 16 alpha)-(+/-)-14,15-dihydro-20,21-dinoreburnamenin-14-ol (vindeburnol, RU 24722) on EEG, on brain energy metabolism and on local cerebral blood flow (LCBF) and in different experimental models of cerebral insufficiency were compared with those of vincamine, vinburnine (1-eburnamonine), dihydroergotoxine mesilate and nicergoline. Vindeburnol at 2 mg/kg i.v., increased the EEG resistance time in rats subjected to asphyxia anoxia and at 10 mg/kg s.c., significantly improved the electrocortical recovery of gerbils subjected to a 10-min cerebral ischemia. Vindeburnol (10 mg/kg i.p.) significantly retarded glucose, phosphocreatine and adenosine triphosphate utilization and lactate production in mouse brain during 10 s of decapitation ischemia. The cerebral metabolic rate was 10.34 mmol/kg/min, which was about 50% of the control value. At 10 mg/kg i.p., the product induced a slight and transient increase in LCBF. Vincamine improved the early phase of the postischemic electrocortical recovery in the gerbil, had no effect on cerebral energy substrates and slightly increased the LCBF for 15 min. Dihydroergotoxine mesilate improved the early phase of the electrocortical recovery in gerbils subjected to ischemia, did not significantly modify the energy substrates and rapidly increased the LCBF, which was normal after 30 min. Vinburnine and nicergoline were inactive in the cerebral insufficiency models used and did not significantly modify cerebral energy metabolism. These results show that vindeburnol has a different pharmacological profile from vincamine, vinburnine, dihydroergotoxine mesilate and nicergoline, and suggest that vindeburnol may be therapeutically effective in cerebral insufficiency.

Topics: Animals; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Cerebrovascular Disorders; Dihydroergotoxine; Electroencephalography; Ergolines; Gerbillinae; Male; Mice; Mice, Inbred Strains; Nicergoline; Rats; Rats, Inbred Strains; Vinca Alkaloids; Vincamine

Concrete cross-sectional studies of the organic brain syndrome, carried out periodically, attempt to establish for the parameters evaluation of substrate damage--and different noopsychopathological rating-scales for the measurement of brain capacity impairment. Beyond the level of the purely correlative-statistical point of view of the relationship between parameter and score changes, demanding for a quantitative model which could provide not only a description, but also an explanation for such a relationship. The fact that there can only be a question here of a "quantitative causality" embracing non-specificity of toxic substances and relative to acute and chronic diffuse organic brain syndromes. It results, that quantitative causality meets the requirements of an exponential function model and that one can validate such models through correlative-statistical methods. This has already been carried out by Ball and Taylor.

Topics: Adult; Aged; Cerebrovascular Disorders; Dihydroergotamine; Dihydroergotoxine; Drug Combinations; Humans; Middle Aged; Neurocognitive Disorders; Psychological Tests; Secologanin Tryptamine Alkaloids; Self-Assessment; Yohimbine

The effect of the alpha-adrenoblockers, nicergoline (N) and dihydroergotoxin (DHET), on the cerebral vessels and the systemic hemodynamics was studied in 152 patients with acute and chronic vascular diseases of the brain. It was established that the hypotensive action of alpha-blockers was the greater the higher was the initial arterial hypertension. REG conducted during an hour after the intravenous administration of N and DHET revealed an increase in the pulse blood filling and an improvement of the arterial tone. Changes in vascular resistance were heterogeneous. Both drugs induced the venous outflow but there were no signs of venous hypotension. An improvement in the systemic and cerebral hemodynamics correlated with clinical improvement.

Topics: Blood Pressure; Brain Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Dihydroergotoxine; Ergolines; Humans; Nicergoline; Plethysmography, Impedance; Subarachnoid Hemorrhage; Vascular Resistance

The effect of DH-ET (dihydroergotoxine = 33% DH-ergocornine (DH-ECO) + 33% DH-ergocristine (DH-ECS) + + 33% DH-ergokryptine (DH-alfa-ECP: DH-beta-ECP = 2:1 and that of the single DH-derivatives on the retention of 14C-uridine (14C-U) in three parts of the brain tissue, blood plasma and liver tissue was estimated (i.e. radioactivity four hours after ip. adm. of 74kBq X 100 g-1). In young male rats DH-ET and DH-ECO enhanced the retention of 14C-U especially in the parietal cortex In one year old males DH-ECS and DH-alfa-ECP had the greatest effect. As a model of undesired effects the influence on peripheral blood flow in the hind limb of urethanised rats was examined using the perfusion' technics. All substances in the dose of 1 microgram removed epinephrine induced vasoconstriction although they themselves in the dose of 100 micrograms enhanced the perfusion pressure, excepting DH-ECO. All substances diminished the liver blood pool in urethanised rabbits (as norepinephrine does), most efficient being DH-beta-ECP and DH-ECO. On the other hand these substances also slowed the velocity of blood stream. The highest toxicity (LD) of DH-ECS and the lowest one of DH-alfa-ECP was found by an infusion technique. All substances diminished heart frequency but had a variable effect on PQ and QT ECG intervals. Ranging all substances according to their desirable properties from the geriatric viewpoint an index for each substance was calculated. This was most advantageous in the case of DH-alfa-ECP and DH-ECS in contrast to DH-ET and DH-ECO.

Topics: Alzheimer Disease; Animals; Cerebral Cortex; Cerebrovascular Disorders; Chinchilla; Dihydroergotoxine; Ergot Alkaloids; Humans; Liver; Male; Mice; Neurocognitive Disorders; Rats; Uridine; Vasoconstriction

Topics: Aged; Cerebrovascular Disorders; Chronic Disease; Dihydroergotoxine; Electroencephalography; Humans; Middle Aged

Dihydroergotoxine mesylate (DHET), an ergot alkaloid derivative, is widely used to treat senile cerebral vascular insufficiency. Aspects of this age-related phenomenon may be due to deterioration by lipid oxidation of cellular membranes. DHET stabilizes EEG alpha frequencies, increases cerebral blood flow and oxygen uptake and accumulates in lipid-rich structures of the brain. The effect of DHET was studied on iron-catalyzed peroxidation of liposomes as measured by the thiobarbituric acid assay. It was found that DHET inhibits peroxidation in vitro in a dose-dependent manner. These results suggest that DHET acts in part as a lipid antioxidant when used to treat senile cerebral vascular insufficiency.

Topics: Cerebrovascular Disorders; Dihydroergotoxine; Humans; Iron; Kinetics; Lipid Peroxides; Liposomes

Topics: Anti-Anxiety Agents; Benzodiazepines; Cerebrovascular Disorders; Cluster Headache; Delayed-Action Preparations; Dihydroergotamine; Dihydroergotoxine; Headache; Humans; Methysergide; Migraine Disorders; Vascular Headaches

A total of 800 physicians practising general medicine, internal medicine and neurology tested the dihydroergotoxin preparation Orphol Drops for a period of six weeks at a daily dose of 30 drops 3 times daily in 8940 patients with cerebrovascular insufficiency. The "cerebral symptom" complex showed the best results with improved findings in 94.5% of cases. The overall assessment of therapy by the doctors in the "psychological findings" complex showed improved findings in 85.7% of the patients affected after 6 weeks' treatment. The third complex, "harmonization of environmental relations" still showed improved findings in 71.6% of the affected patients. The sustained improvements in all three "complexes" were striking, also in the second period of the trial, which emphasizes the importance of longterm therapy of deficiency symptoms in cerebrovascular insufficiency.

Topics: Aged; Anxiety Disorders; Cerebrovascular Disorders; Cognition Disorders; Depression; Dihydroergotoxine; Drug Administration Schedule; Drug Tolerance; Headache; Humans; Hypoxia; Memory; Vertigo

Topics: Aged; Arterial Occlusive Diseases; Cerebrovascular Disorders; Cyclandelate; Dihydroergotoxine; Female; Humans; Isoxsuprine; Leg; Male; Vasodilator Agents

After setting up a catalogue of complaints and signs for the most frequent disturbances of feeling tone of the patients suffering from cerebral arteriosclerosis, consisting of somatically subjective head pain and mental disturbances, treatment was given to 33 patients with cerebrovascular disturbances and 7 patients with similar, although non-vascular, disturbances (4 patients with presenile dementia, 3 patients with tinnitus in otosclerosis), the treatment consisting of eutergin 3 X 1 tablets to 3 X 2 tablets daily, the concomitant cardio-internistic medication remaining the same throughout the treatment course. The type and severity of the symptoms prevailing in each case were determined at the beginning, after 3 weeks and after 6 weeks of the medication with eutergin. It was found that improvement of the somatic-subjective head pain was more pronounced than that of the mental disturbances. Generally speaking, the disturbing somatic or mental signs were those which could be influenced better than the others. As far as the head pain was concerned, the feeling of giddiness, congestion in the head, rapid exhaustion, above all, tinnitus, responded best to the medication (the improvement amounting to approximately 40%), whereas of the mental complaints, a feeling of being "lost" or "abandoned" and a morose mood were most amenable to improvement (degree of improvement approximately 30%). The prevention of the delirogenic effect of antidepressives in senile depression was a remarkable effect; this means that effective antidepressive medication is made possible with the help of eutergin, EEG controls did not reveal any significant effects. There were no side effects. Elevated blood pressure levels showed a tendency to become normal without any dramatic drops. Hence, eutergin is recommended in all kinds of chronic cerebrovascular lesions, provided it is associated with concomitant cardiac and internistic treatment.

Topics: Aged; Antidepressive Agents; Cerebrovascular Disorders; Chronic Disease; Dementia; Dihydroergotoxine; Drug Combinations; Electroencephalography; Headache; Humans; Mental Disorders; Middle Aged; Neurocognitive Disorders; Otosclerosis; Papaverine; Sparteine; Tinnitus

Topics: Aged; Cerebral Cortex; Cerebrovascular Disorders; Dihydroergotoxine; Electroencephalography; Ergoloid Mesylates; Humans; Male; Middle Aged; Placebos

The adrenergic control of the cerebral circulation was subjected to pharmacological analysis. The status of the cerebral circulation was assessed using radioisotope, electromagnetic and resistographic methods. EEG, ECG and arterial pressure were recorded. The acid-base equilibrium and oxygen tension were measured in the arterial blood and cerebrospinal fluid. The experiments showed that the sympathetic innervation plays an important role in controlling cerebral circulation and in the development of cerebrovascular disorders. This was indicated by the constriction of intracranial arteries induced by noradrenaline, stimulation of sympathetic nerves, reflex sympathetic activations and the effect of potassium chloride on the centrol nervous system. The pharmacological study demonstrated that constriction of the intracranial vessels is brought about by an activation of the sympatho-adrenal system which is mediated via alpha-adrenoreceptors of cerebral blood vessels.

Topics: Acid-Base Equilibrium; Animals; Blood Pressure; Cats; Cerebrovascular Circulation; Cerebrovascular Disorders; Dihydroergotoxine; Dogs; Electric Stimulation; Guanethidine; Hydrogen-Ion Concentration; Nialamide; Norepinephrine; Partial Pressure; Phenoxybenzamine; Potassium Chloride; Propranolol; Vasomotor System

Topics: Adult; Arterial Occlusive Diseases; Cerebrovascular Disorders; Dihydroergotamine; Dihydroergotoxine; Drug Combinations; Ergoloid Mesylates; Ergotamines; Extremities; Humans; Male; Middle Aged; Secologanin Tryptamine Alkaloids

Topics: Aged; Bradycardia; Cerebrovascular Disorders; Dementia; Dihydroergotoxine; Ergoloid Mesylates; Female; Humans; Male

Topics: Aged; Aphasia; Brain; Cerebral Hemorrhage; Cerebrovascular Disorders; Dihydroergotoxine; Ergoloid Mesylates; Female; Hemiplegia; Humans; Intracranial Arteriosclerosis; Intracranial Embolism and Thrombosis; Male; Middle Aged; Vertigo

Topics: Blood Flow Velocity; Cerebrovascular Circulation; Cerebrovascular Disorders; Dihydroergotoxine; Drug Combinations; Ergoloid Mesylates; Humans; Plethysmography, Impedance; Yohimbine

Topics: Cerebrovascular Disorders; Dihydroergotoxine; Drug Therapy; Ergot Alkaloids; Geriatrics; Humans; Paraplegia; Spinal Cord; Vascular Diseases

Topics: 4-Aminobenzoic Acid; Cerebrovascular Disorders; Dihydroergotoxine; Drug Combinations; Ergot Alkaloids; Humans; Procaine; Sulfonic Acids

Topics: Arteriosclerosis; Biomedical Research; Cerebrovascular Disorders; Dementia; Dihydroergotoxine; Ergoloid Mesylates; Ergot Alkaloids; Geriatrics; Humans; Hypertension; Intracranial Arteriosclerosis; Psychotic Disorders; Toxicology

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Bronchopneumonia; Cerebral Hemorrhage; Cerebrovascular Disorders; Dicumarol; Dihydroergotoxine; Ergot Alkaloids; Femoral Neck Fractures; Fracture Fixation; Heparin; Mortality; Myocardial Infarction; Neoplasms; Phenindione; Preventive Medicine; Pulmonary Embolism; Surgical Procedures, Operative; Sweden; Thromboembolism

Topics: Benzoates; Biomedical Research; Cerebrovascular Disorders; Dihydroergotoxine; Drug Therapy; Ergot Alkaloids; Leucine; para-Aminobenzoates; Stroke; Toxicology; Vasodilator Agents