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Results for “Vinca Alkaloids”

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At least 19 recordsLinked to original sources
PubMed1979

Correlation of the clinical neurotoxicity of the vinca alkaloids vincristine, vinblastine, and vindesine with their effects on cultured rat midbrain cells.

Clinical experience with three vinca alkaloids currently in use as antineoplastic agents has shown a difference in the degree of peripheral neurotoxicity manifested by these compounds: vincristine greater than vindesine greater than vinblastine. This phenomenon may reflect differences in pharmacokinetics and/or the differential response of the nerve tissue itself. Differences in pharmacokinetics can be avoided by studying the direct effects of the vinca alkaloids on primary cultures of neuronal and glial cells. Vincristine at a dose as low as 0.004 microgram/ml affects the cells with processes in cultures of dissociated newborn rat midbrain. In 3-day-old cultures, after 24 h of drug treatment there is a loss of processes and swelling of the cell body. We have used this observation as the basis for a quantitative assay of the toxicity of a series of vinca compounds, and have found that for a dose range of 0.1--0.004 microgram/ml the relative toxicity of vincristine, vinblastine, and vindesine in this system correlates with their relative clinical neurotoxicity. Validation of the predictive elements of this system awaits clinical experience with novel vinca compounds.

Animals↗
PubMed1977

Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on axonal fibrillar organelles in vitro.

Axonal ultrastructural changes induced by three Vinca alkaloids, vincristine, vinblastine, and desacetyl vinblastine amide, were studied in vitro at concentrations of 0.01, 0.05, and 0.1 mM in the cat vagus nerve. Disruption of microtubules, appearance of paracrystalline structures, and increase in neurofilaments were induced by all three agents at 0.1 mM. A new type of paracrystal with an electron-dense central core in each subunit was also observed with each drug. Whereas all three compounds affected unmyelinated fibers (vinblastine more so than the other two), only vinblastine significantly damaged the myelinated fibers. The greater effectiveness of vinblastine in causing these in vitro ultrastructural changes contrasts strikingly with the clinical in vivo situation in which vincristine is the most neurotoxic. This suggests that clinical neurotoxicity is associated with additional factors aside from the direct interaction of the Vinca alkaloids with microtubules or tubulin.

Animals↗
PubMed1978

A comparison of the antifertility effects of alkylating agents and vinca alkaloids in male rats.

1 The anti-fertility effects of cyclophosphamide, nitrogen mustard, vincristine and vinblastine were studied and compared in male rats. 2 The effects of the drugs on body weight and haematological values were used to monitor the pharmacological actions of the drugs. 3 All four drugs impaired fertility, the severity of the impairment depending on dose and duration of treatment. 4 Testicular size and histological appearances remained mostly normal, even in infertile animals, but seminiferous tubules were fewer in number and maturation arrest at the spermatid level was evident in some sections. 5 Recovery of drug-induced infertility occurred in 64% of treated animals, 9 to 40 weeks after cessation of treatment. 6 Morbidity and mortality were much higher with alkylating agents than with vinca alkaloids for approximately similar degrees of impairment in fertility.

Alkylating Agents↗
PubMed1979

A study of the effect of vinca alkaloid 'vinblastine' on gastrointestinal motility in rats.

Vinblastine an alkaloid of the periwinkleplant (Vinca), produced marked alterations in the motility of gastrointestinal tract in rats. The alkaloid reduced the rate of gastric emptying and slowed the transit of test substance through the small intestine. The effect of the drug on gastric emptying appeared to be dose-dependent. The latency of drug action on gut motility was found to be 5--10 min, when injected through the jugular vein.

Animals↗
PubMed1979

Animal models for the comparative assessment of neurotoxicity following repeated administration of vinca alkaloids.

Neurotoxicity is the major side effect occurring during the clinical use of vincristine (VCR). Animal models predictive of potential neurotoxicity would be very useful in the preclinical development of new vinca compounds. To simulate conditions in which neurotoxicity is produced during the clinical use of VCR, experimental animals (except the guinea pig) were given the test compounds by the iv route over a prolonged time period. Doses were selected based on the production of leukopenia. Vindesine (VDS), a chemically modified vinblastine (VBL) product, was compared with VCR and VBL in animal studies. Definite neurotoxic manifestations developed when VCR was given to chickens, cats, and monkeys. The administration of VDS or VBL did not produce neurotoxic signs in these species. The mouse, rat, dog, and guinea pig were not found to be useful models. Thus, it would appear the chicken, cat, and monkey would be appropriate animal models for the preclinical testing of new vinca compounds.

Animals↗
PubMed1977

Alkaloids of Vinca rosea L. (Catharanthus roseus G. Don). 38. 4'-Dehydrated derivatives.

A series of 4'-dehydrated derivatives of various dimeric Vinca alkaloids has been synthesized to further define the structure-activity relationships of Vinca alkaloids with onolytic potency. The concentrated sulfuric acid dehydration in most cases gave mixtures of the 3',4'-and two isomeric 4',20'-alkenes, which were isolated and characterized primarily by proton and 13C NMR. Compound tested for antitumor activity include the three dehydro isomers of 4'-deacetylvinblastine, 4-deacetylvincristine, and 4-deacetylvinblastine-23-amide and some4'-dehydrated derivatives epimeric at C-18'. Generally, the decrease in toxicity imparted by the new double bond was accompained by a decrease in potency. An exception was 3',4'-dehydro-4-deacetylvincristine, which showed a decrease in toxicity and increase in potency against at least one tumor in which vincristine itself has little effect.

Adenocarcinoma↗
PubMed1978

The treatment of idiopathic thrombocytopenia with vinblastine-loaded platelets.

We devised a method to enhance delivery of vinblastine to macrophages, the cells believed to be responsible for platelet destruction in idiopathic thrombocytopenic purpura. Our strategy was based on the ability of platelets to bind vinca alkaloids such as vinblastine. Platelets were incubated with an excess of vinblastine, concentrated and then, after excess alkaloid had been removed, given to 11 patients with idiopathic thrombocytopenia refractory to other treatment (including intravenous injections of vinca alkaloids). Platelet antibodies in the patients' plasma led to ingestion of the vinca-laden platelets by macrophages. There were six complete remissions, three partial remissions and two failures. Side effects in a few patients, reversible but annoying, were minimized as technics were refined. We conclude that in patients with idiopathic thrombocytopenia refractory to all other measures, including the use of vinca alkaloids, platelet-vinca complex may be effective.

Adolescent↗