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PubMed1984

Pharmacokinetic study of vincamine teprosilate.

The results obtained by the authors in the pharmacokinetic study of vincamine teprosilate after oral and i.v. administration to young healthy volunteers and after oral administration to patients aged 68 to 84 years are presented. The description of the assay for each administration route is reported in the protocol. Plasma levels of vincamine teprosilate were assayed by reverse phase HPLC with spectrofluorimetric detection. The data obtained after i.v. administration made it possible to define the pharmacokinetic model and to estimate parameters. Concentration-time data were adapted to a biocompartmental open model with alpha value of 2.9080 and beta value 0.1047. In oral administration, the overlapping of the fast disposition phase and the absorption phase led to an apparent monocompartmental fit; in both young and aged volunteers, the absorption rate constants as well as the elimination rate constants were calculated. In both groups no significant differences in tmax values were found and no latency period was noticed . Cmax values were similar in both groups of patients; the lower distribution volume in aged volunteers compared to younger ones contributed to this finding. Differences in absorption rate constants in aged and young volunteers (0.53 h-1 and 0.73 h-1 respectively) are analysed. Vincamine teprosilate bioavailability after oral administration was found to be 20 +/- 5%. Possible vincamine teprosilate dose dependence kinetics are suggested.

Administration, Oral↗
PubMed1984

Pharmaco-EEG study on vincamine and on teproside in patients with chronic cerebrovascular disease.

Pharmaco-EEG is a technique used in diagnostic and in neuropharmacological research. Correlations between the ageing brain and EEG spectral analysis have been discovered (1-5). Typical EEG findings of multi-infarct dementia, senile dementia and chronic cerebrovascular disease have been reported by several authors. Using this methodology, it is possible to know if a drug crosses the blood brain barrier, the period of drug action and the drug-induced enhancement or inhibition of cerebral bioelectrical activity. It is also possible to ascertain the pharmacological class of a drug through a comparison between it and another that is well known. The authors have studied the pharmaco-EEG effects of teproside and vincamine in two groups of subjects affected by chronic cerebrovascular disease. The first group (8 patients, mean age 58.3 years) were treated with vincamine 15 mg i.v. EEG spectral analysis was performed using a Hewlett-Packard 5423 A analyser with centro-occipital derivations. EEG registrations were executed by using an epoch of 5 min at times- 15, 0, +15, +45, +60, and +120 min with drug administration at zero time. In a chronic study, after a three day wash-out period, teproside 240 mg/os/day was administered to the first group, while vincamine 60 mg/os/day and 120 mg/os/day was administered to the second group. Subjects were studied with EEG spectral analysis by using the same methodology at baseline and after 10 and 20 days of treatment. The two drugs induced an enhancement of cerebral bioelectrical activity by an improvement of alpha waves mean relative power, by a shifting toward rapid rhythms of dominant frequency and by a decrease of delta and theta waves mean relative power. With the dosages used teproside appeared to be more active than vincamine.

Aged↗
PubMed1984

The effects of vincamine on experimental cerebral infarction in Mongolian gerbils: a pilot study.

Unilateral ligation of the common carotid artery was performed in 134 gerbils. Study I was comprised of 60 controls and 60 animals receiving I.P. vincamine 1 mg/kg q4h. In a small second study 14 animals received vincamine I.P. 40 mg/kg q12h. In all groups ligation of the carotid artery was performed 6 days after starting dosing. The animals were observed for a further 6 days after carotid artery ligation. Whereas vincamine had no effect on the percent of animals in each group dying after carotid ligation, the extent of stroke lesion, measured histometrically, was significantly reduced (P less than 0.05) in the vincamine treated animals.

Animals↗
PubMed1978

[Metabolism of vincamine in the rat].

The metabolism of vincamine hydrochloride was studied in the rat after oral administration of the drug. Vincamine is almost completely metabolized, only a small fraction of the original compound being excreted in the urine. The metabolites detected in blood, urine and tissues were purified by preparative thin layer and column chromatography in several solvent systems, and analyzed by mass spectrometry. It was found that the main urinary metabolites were vincamine conjugates (sulphates and glucuronides). Two new metabolites were detected in all the biological fluids and specimens analyzed: these compounds are more polar than vincamine and their structure was characterized by mass spectrometry, I.R. and U.V. spectroscopy and confirmed by synthesis in our laboratory.

Animals↗
PubMed1978

[Demonstrating the effectiveness of cerebroactive drugs in aged patients. Results of a randomized double-blind study of a vincamine containing special preparation].

The neuropsychiatric symptoms of old patients with disturbed cerebral metabolism or blood flow mostly lead to great individual difficulties and make those patients difficult to handle: in the family as well as in hospital such patients develop alienation, isolation and therefore adaptation to a social structure deteriorates with time. In the course of a test program for medicinal therapy of this syndrome we studied the efficacy of a vincamine containing formulation (Pervincamin forte retard or Pervincamin ampoules, respectively) on the symptoms of a chronical brain disturbance. The study was randomised double-blind. We found that under the influence of the vincamine formulation the subjective symptoms, such as lack of interest, apathy, aggressiveness, raging, psychomotoric retardation, lack of concentration, dysmnesia, decreased with a statistical significance (p less than or equal to 0.05). Also the subjective symptoms, reported by the patients, such as tinnitus and vertigo decreased significantly under the treatment with the vincamine preparation. Therefore some of the parameters important for resocialisation and revitalisation of old patients could be influenced in a favourable way. Basing on the good results of our investigations, the treatment of psychiatric disturbances in old patients with vincamine containing drugs seems to be justified.

Aged↗
PubMed1977

[Vincamine concentrations in plasma and cerebrospinal fluid in patients following intravenous infusion (author's transl)].

The pharmacokinetic characteristics of 14,15-dihydro-14beta-hydroxy-(3alpha,16alpha)-eburnamenine-14-carbonic acid methylester (vincamine; Vincapront) were studied after i.v. infusion (30 or 40 mg vincamine-hydrochloride within 28--40 min, respectively) in 6 patients with cerebrovascular diseases. At the end of the infusion, maximum plasma levels ranged between 607 and 999 ng/ml. The decline of the plasma concentrations after the end of the infusion could be described using a two-compartment open model. After a phase of distribution lasting 1--2 h there was a linear elimination of vincamine in the semilogarithmic plot. The mean half-life for the beta-slope was 2 h. In four patients we measured the vincamine concentration in the cerebrospinal fluid 2 h after the end of the infusion. It amounted to only 5--24% of the simultaneously estimated plasma concentration.

Adult↗
PubMed1977

[The influence of vincamine on global and regional cerebral blood flow in acute and subchronic human cerebral ischimia (author's transl)].

The alterations in global and regional cerebral blood flow (CBF) following i.v. application of 14,15-dihydro-14beta-hydroxy-[13alpha,16alpha]-eburnamenine-14-carbonic acid methylester (vincamine) were studied in 18 patients suffering from acute or subchronic cerebral ischemia. CBF measurements were made after intra-arterial injection of 133Xe using a multi-detector measuring instrument. 30 sec after a single i.v. application of 30 mg/20 min vincamine a statistically significant increase of CBF by 1.5 ml/100 g/min was found, corresponding to 6.1% (p less than 0.01). The regional CBF was influenced to a varying degree, the areas marked by an insufficient blood supply showing a mean increase by 13.4% and the areas marked by normal basic values showing a mean increase by 5.3%. This difference in alteration is statistically significant (p less than 0.02) comparing the differences as percent. The duration of the action of vincamine on the CBF, after a single dose of 30 mg/20 min i.v., was determined for a maximum of 15 min. The CBF values measured within 15 min after the completed i.v. application of vincamine showed a mean decline in blood flow values by --2.5 ml +/- 7.4%, which is statistically insignificant.

Acute Disease↗
PubMed1984

The effects of bromvincamine and vincamine on regional cerebral blood flow and mental functions in patients with multi-infarct dementia.

The effects of vincamine and bromvincamine (BV 26-723) on mental functions and regional cerebral blood flow (rCBF) measured by the 133Xe inhalation method, were investigated in ten patients with mild to severe symptoms of multi-infarct dementia. The double blind cross over design included three treatment periods, each of 2 weeks' duration. The patients were drug free at the time of the first investigation in each treatment period. Then placebo, vincamine or bromvincamine was given orally (4 X 20 mg/day). Psychiatric evaluation, psychometric assessment and measurement of rCBF were done at start of medication and after 1 and 2 weeks during medication. There were 2 drug-free weeks between the first and second, and second and third treatment periods. Results from treatment with vincamine showed a significant increase in the global CBF level and reduction of initial right-left asymmetry of hemispheric means. No effects were seen in regional flow patterns. Performance score on a verbal memory test increased significantly. No significant effect on the global rCBF level was indicated for bromvincamine. However, the number of ischemic regions decreased significantly during treatment. Performance on two memory tests improved significantly. No significant changes in overall psychiatric ratings were observed for any of the treatment periods.

Aged↗
PubMed1982

The effect of vincamine, hydergine and piracetam on the firing rate of locus coeruleus neurons.

Vincamine, hydergine and piracetam are used for the treatment of memory disturbances as well as for the treatment of various other brain dysfunctions seen in the elderly patient. The action of these three psychogeriatric compounds on the activity of noradrenergic neurons in the rat locus coeruleus was investigated. All three compounds, when administered intraperitoneally, increased the firing rate of noradrenergic neurons in the chloral hydrate anaesthetized animals. Vincamine and hydergine had a similar potency producing a maximal mean increase of about 70% at a dose of 1 mg/kg. Likewise, piracetam was significantly less potent eliciting a 30 to 40% increase in firing at doses of 300 and 1000 mg/kg, respectively. A role for the locus coeruleus in processes related to attention, cortical and behavioral arousal, learning and memory has been proposed on the basis of behavioral and electrophysiological experiments. In the awake rat, the firing rate of noradrenergic neurons in this brain nucleus has previously been shown to relate directly to the level of vigilance. The activating action of vincamine, hydergine and piracetam on these neurons may be linked with some of the drugs' beneficial therapeutic effects.

Animals↗
PubMedDate not supplied

Pharmacokinetics and metabolism of vincamine and related compounds.

The pharmacokinetics and metabolism of vincamine, vinpocetine, methylene-methoxy-apovincaminic acid ester and eburnamine have been reviewed. The main route of elimination for vincamine, vinpocetine and methylene-methoxy-apovincaminic acid ester is ester cleavage and conjugation in the case of eburnamine. Vincamine and its derivatives show significant differences in metabolic pathway and their elimination is rapid in the species studied. Emphasis has been placed on the analytical methods used for monitoring these drugs in biological systems.

Animals↗
PubMed1980

Effects of vincamine on EEG sleep patterns in man: a pilot study.

Nightly EEG recordings were performed in 8 healthy volunteers after intramuscular injections of placebo and 30 mg vincamine, under double-blind conditions, according to a crossover design. The single dose of vincamine induced a significant decrease in sleep Stage 4, a decrease in REM stages which approached statistical significance, and finally an increase in REM latency only in subjects showing low baseline values of this parameter. The above data confirm the awakening and antidepressant action of vincamine observed in previous studies in both animals and man.

Adult↗
PubMed1978

Influence of vincamine and piracetam on sleep--waking pattern of the cat.

The effect of Vincamine and Piracetam, two geriatric drugs, on sleep behavior of the laboratory cat was studied. The animals were chronically prepared for recording of the EEG of the cerebral cortex, the lateral geniculate body, and the hippocampus, and for recording of eye movements, the muscular tonus and respiration. During the experiment, sleep and waking behavior were monitored by the above mentioned telemetrically transmitted indicators and also through observation via closed-circuit television. Both Vincamine and Piracetam in doses of 1 and 300 mg/kg p.o., respectively, enhance absolute and relative amounts of paradoxical sleep (PS). Smaller doses have a lesser or no effect on PS. Larger doses again have little effect or else, in the first few hours after application, reduce PS and total amount of sleep. Both drugs have little effect on slow wave and total sleep. Piracetam, but not Vincamine, reduces the prominent frequency of the theta band in hippocampus during PS. The PS-enhancing effect of the two geriatric drugs may be related to their memory-improving influence.

Animals↗
PubMed1986

A comparison of some of the pharmacological properties of the new eburnamenine derivative vindeburnol with those of vincamine, vinburnine, dihydroergotoxine mesilate and nicergoline.

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.

Animals↗
PubMed1978

Comparative study of the clinical effects of vincamine + glycerol versus glycerol + placebo in the acute phase of stroke.

The treatment of the acute phase of stroke creates a difficult problem to the clinician. The presently used drugs lead to controversial results. The progress in knowledge of the pathogenesis of cerebral damage underlines the determinant role of the metabolic deficits in the ischemic areas. The effect on the clinical symptomatology of patients in the acute phase of stroke was studied during a double-blind comparative clinical trial with an alcaloid of Vinca minor (Pervincamine) which acts favorably against disturbances of oxydative glucose metabolism and of cerebral microcirculation. 20 patients divided into two homogeneous groups received during 5 days either Pervincamine (4 ampoules of 3 ml = 60 mg vincamine p.d.) + glycerol, or glycerol + placebo administered by i.v. infusion. Clinically the results indicate a greater improvement of the neurological status (objectivated by a neurological scale) with vincamine treatment than with placebo. Statistically the analysis confirms the highly significant effect of vincamine on motility of lower and upper limbs (p less than 0.02) and the significant effect on cranial nerves (homonymous hemianopsia and conjugated deviation of eyes) (p less than 0.05) and on the sphincter control level (p less than 0.05).

Adult↗
PubMed1984

Cerebral antioedematous effect of Teproside and of some vincamine derivatives.

Alkyltin compounds are known to produce in the rat a selective oedema of the CNS, especially of the white matter. Vincamine and vincamine derivatives, among which Teproside is the most potent, are able to prevent the occurrence of such an oedematous reaction whereas xanthine derivatives and papaverine fail to prevent this oedema. It is suggested that there may be a potentiation of the effect of vincamine by the xanthine part of the Teproside chemical structure.

Animals↗
PubMed1975

Effects of vincamin on cerebral metabolism.

In this study the effects of vincamin (Pervincamine) on cerebral metabolism were investigated. 60 subjects were tested. Vincamin was administrated to 36, aminophillin to 12. No drug was given to the remaining 12 subjects who were used as controls. A definite increase in cerebral metabolism was observed in patients receiving vincamin either by intravenous or intramuscular injection. Practically no change in cerebral metabolism was detected in subjects treated with aminophyllin.

Adolescent↗
PubMed1975

[Vincamine in patients with cerebral vascular insufficiency].

The effects of the treatment with vincamine in 20 patients with cerebral vascular insufficiency are reported. The patients were previously submitted to the following tests: neurologic examination, electroencephalography, laboratory tests, psychometry (memory, intellective capability, concentrated attention, abstract reasoning and personality tests). Patients were medicated with vincamin in a 40 mg dose within 24 hours during approximately a 150 days period, after which were again submitted to an identical analysis. The results obtained revealed that in a reasonable percentage of the cases vincamin is an useful medication in controlling the clinical manifestations of the cerebral vascular insufficiency, an improvement being demonstrated in the retrograde and anterograde deficit rate observed in objective tests. An improvement was also noticed in the electroencephalograpric pattern of a few patients.

Adult↗
PubMedDate not supplied

[Effect of vincamine, vinervine and serotonin on the sexual cycle in rats].

With a prolonged enteral introduction indole alkaloids vincamine (5--20 mg/kg), vinervine (5 mg/kg) and serotonin (2 mg/kg) significantly lengthen the duration of the sex cycle through extending the estrus cycle (vincamine, vinervine and serotonin) and diestrus (serotonin). Without changing the weight of the uterus the studied alkaloids tend to significantly increase the weight of the ovaries and the number of follicles therein. In test with sexually mature castrated and also sexually immature (both alkaloids) and hypophysectomized (vincamine) animals these alkaloids fail to display any estrogenic action.

Animals↗