Linnea extracts and manufactures Vincamine as a botanical ingredient for pharmaceutical purposes.
Vincamine is a plant alkaloid first extracted in industrial quantities in 1955 by a team of scientists investigating on agents with vasoactive properties. They found that agents with indolic skeleton selectively improve the cerebral blood supply and introduced their use in the treatment of cerebrovascular disorders .
The increasing percentage of elderly individuals suffering from age-associated cognitive impairment and the lack of effective medical treatment have become a major health concern due to the large number of individuals experiencing dementia. Eighty percent of elderly individuals in North American and European populations show signs of cerebrovascular disease and mixed vascular cognitive impairment with a risk of regression to Alzheimer disease and dementia.
Many conditions of cognitive decline share common causative or contributory factors. The principal causes of a progressive decline in brain function are decreased cerebral blood flow, insufficient cerebral circulation, and a reduction in cerebral metabolism and oxygen utilization. Vincamine was the first natural ingredient found to be effective in retarding the effects of the multiple mechanisms and factors responsible for cognitive decline.
The Apocynaceae plant family contains a large number of eburnamine-vincamine alkaloids. Vincamine can be found in the aerial part of the Vinca minor plant, the Voacanga africana and the Crioceras longiflorus.
The Linnea Vincamine production process is based on synthesis from the Tabersonine derivative of Voacanga africana. Voacanga africana is a tropical, evergreen tree with yellow or white flowers, that grows up to a height of around 6 m. Native to the West African rainforests, it prefers well composted rich soils in a protected sunny to partly shaded position, and is sensitive to drought and frost.
Voacanga africana is well known to African magic healers although little is known about the actual use of the seeds and bark of the various Voacanga species other than the fact that the plant is held in high esteem for ritual purposes.
The Voacanga seeds are carefully harvested through a selected network of suppliers. Each shipment leaving West Africa is inspected previously by a Linnea representative so as to ensure raw materials of the highest quality all over the world.
Vincamine carries out various pharmacological activities on cell multiplication, in the central nervous system and in the cardiovascular system, but its main activity concerns the blood vessels in the brain [2,3]. Vincamine provides a modulatory effect on the cerebral circulation and neuronal homeostasis that result in various degrees of antihypoxic and neuroprotective potency .
The neuroprotective effect of Vincamine is induced by several changes in the maximum levels of some energy transducing enzymes (lactate dehydrogenase; citrate synthetase and malate dehydrogenase; total NADH-cytochrome c reductase and cytochrome oxidase) as a function of the duration of ischaemia [5, 6].
According to Benzi and collaborators (1982), Vincamine also modulates catecholamines and serotonin levels, decreasing the activity of acetylcholine esterase in the occipital area .
Common Applications and Evidence
The neurological and psychiatric symptoms of elderly patients with altered cerebral metabolism or blood flow lead mostly to major individual difficulties, making these patients difficult to handle: both at home and in hospital such patients become aliened, isolated and therefore find it progressively more difficult to adapt to a social institution. Vincamine can have a favourable influence on some of the parameters important for the resocialisation and revitalisation of elderly patients [2,3]. Due to its ability to increase cerebral blood flow, oxygen consumption and glucose utilization, Vincamine is used in the treatment of chronic cerebrovascular ischemia and in a number of brain disorders of elderly patients, such as memory disorders, vertigo, transient ischemic deficits and headache including various forms of dementia. Beneficial effects have been also reported in the treatment and prevention of acute ischemic strokes and in the treatment of tinnitus and hypertension.
The therapeutic efficacy of Vincamine has been clinically assessed on the basis of both neuro-psychological criteria (memory tests, perceptive-spatial and logical function tests) adopted in evaluating mental function and the measurement of changes in the regional cerebral blood flow .
Acute and chronic cerebrovascular disorders
Italian researches demonstrated the efficacy of Vincamine in a placebo controlled trial involving patients with chronic cerebrovascular disorders selected at the Montescano Medical Rehabilitation Centre. After a two-week wash-out period one patient group was treated with 120 mg per day for a period of 90 days. The results obtained showed a significant improvement in behavioural performance, mnemonic ability and perceptive-motor activity in the group treated with Vincamine .
The authors also investigated the brain electrical activity measuring the EEG changes in accordance with a double-blind randomized schedule. A dual effect was observed: an early effect, i.e. an improvement in the EEG pattern within an hour of administration; and a later effect preventing negative EEG modifications from taking place at the fourth hour following administration [10,11].
Cognitive functions and degenerative senile cerebral dysfunction
The therapeutic efficacy of Vincamine was clearly confirmed in the treatment of primary degenerative and vascular dementia demonstrated in a double-blind clinical trial involving 152 patients aged 50-85. The clinical importance of the outcome was further underlined by the results collected according to Clinical Assessment Geriatric subscale ‘need for help’ of the nurse’s rating of geriatric patients (Beurteilungsskala für geriatrische Patienten; BGP) and the Short Cognitive Performance Test (Syndrom-Kurztest; SKT) . The effects of Vincamine on mental functions (psychiatric evaluation and psychometric assessment) and regional cerebral blood flow (rCBF) were measured by the 133Xe inhalation method in ten patients with mild to severe symptoms of multi-infarct dementia. Results showed a significant increase in the global CBF level and reduction in initial right-left hemispheric asymmetry. The performance score in a verbal memory test increased significantly [13,14].
|Name of the plant
|Part of the plant used
||(3α,14β,16α)-14,15-dihydro-14-hydroxyeburnamenine-14-carboxylic acid methyl ester.
- Investigation of vasoactive agents with indole skeletons at Richter Ltd. Acta Pharm Hung. 2002;72(1):25-36. Kárpáti E, Bíró K, Kukorelli T.
- Vincamine: a psychogeriatric agent blocking synaptic potentiation in hippocampus. Life Sci. 1982 Nov 1;31(18):1947- 53. Olpe HR, Barrionuevo G, Lynch G.
- The Complete German Commission E Monographs. Boston, MA, American Botanical Council, 1998 pp. 364-365 . Blumenthal, M., ed.
- Eburnamine derivatives and the brain. Med Res Rev. 2005 Nov;25(6):737-57. Vas A, Gulyás B.
- Effect of ischaemia and pharmacological treatment on enzyme activities of cortical mitochondria and synaptosomes. Int J Clin Pharmacol Res. 1984;4(4):263-75. Villa RF, Gorini A
- Study on the anti-hypoxic effect of some drugs used in the pharmacotherapy of cerebrovascular disease. Methods Find Exp Clin Pharmacol. 1983 Nov;5(9):607-12 Milanova D, Nikolov R, Nikolova M
- Relation of Direct Vascular Activity to Cerebral Blood Flow J Cereb Blood Flow Me/abol, Vol. I, No. I. 1981 (1982) Farmaco Ed. Sci., 36(Sept), 811-816 Benzi, G., Arrigoni, E., Pastoris, O., Marzatico, F., Curti, D. Et al.
- Therapeutic efficacy of Vincamine in dementia. Neuropsychobiology, 34(1), 29-35 (1996) Fischhof, P.K., Moslinger-Gehmayr, R., Herrmann, W.M., Friedmann, A. & Russmann, D.L.
- Evaluation of the effect of Vincamine teprosilate on behavioural performances of patients affected with chronic cerebrovascular disease. Int J Clin Pharmacol Res. 1984;4(4):313-9. Casale R, Giorgi I, Guarnaschelli C
- Acute i.v. Vincamine teprosilate administration: quantified investigation in elderly subjects. Int J Clin Pharmacol Res. 1984;4(4):303-6. Moglia A, Alfonsi E, Zandrini C, Pistarini C, Arrigo A
- Pharmaco-EEG study on Vincamine and on teproside in patients with chronic cerebrovascular disease. Int J Clin Pharmacol Res. 1984;4(4):291-302. Martucci N, Manna V, Agnoli A
- Therapeutic efficacy of Vincamine in dementia. Neuropsychobiology. 1996;34(1):29-35 Fischhof PK, Möslinger- Gehmayr R, Herrmann WM, Friedmann A, Russmann DL. (Blumenthal, 1998; Fischhof et al., 1996; Olpe et al., 1982).
- The effects of bromVincamine and Vincamine on regional cerebral blood flow and mental functions in patients with multiinfarct dementia. Psychopharmacology (Berl). 1984;83(4):321- 6. Hagstadius S, Gustafson L, Risberg J
- A new approach to the treatment of patients with circulatory encephalopathy. Lik Sprava. 1997 Sep- Oct;(5):142-5. Kupnovyts’ka MIu, Lushchyk UB, Herasymchuk RD, Chmyr HS, Iatsyshyn RI, Dubanovych LB
- Demonstrating the effectiveness of cerebroactive drugs in aged patients. Results of a randomized doubleblind study of a Vincamine containing special preparation. Arzneimittelforschung. 1978;28(1):90-4. Foltyn P, Groh R, Lücker PW, Steinhaus W.
- EMEA (1999) Committee for Veterinary Medicinal Products Vincamine Summary Report. Document EMEA/MRL/587/99- FINAL. European Agency for the Evaluation of Medicinal Products (EMEA), Veterinary Medicines Evaluation Unit [http:// www.emea.eu.int/pdfs/vet/mrls/058799en.pdf]. Searched November 18, 2002
- Effects of Vincamine on the mesenteric circulation in the rat Farmaco Ed. Prat., 33, 326-332 (1978) Piacenza, G. & Pesce, E.
- Respiratory effects of Vincamine hydrochloride. Farmaco Ed. Prat., 33, 319-325 (Abstract) (1978) Piacenza, G. Pesce, E. & Marchini, F.