Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nabilone is a new orally active cannabinoid for the treatment of severe gastrointestinal toxicity associated with cancer chemotherapy. The pharmacological profile of nabilone suggests that it acts primarily by preventing emesis controlled by the medulla oblongata, although its secondary mild anxiolytic activity may contribute to the overall efficacy. Nabilone 2mg twice daily starting 12 hours prior to, and continued for the duration of, chemotherapy produces significant reduction in the severity and duration of nausea and the frequency of vomiting in about 50 to 70% of patients with severe symptoms refractory to conventional therapy. Nabilone has proven to be more effective in controlling symptoms and preferred by more patients than prochlorperazine 10mg 2 to 4 times daily in a limited number of studies, despite a higher incidence of side effects. Comparative trials against other new antiemetic agents, such as high dose metoclopramide, and use of nabilone in combination with other antiemetics remain to be undertaken. The incidence of side effects is high with nabilone; drowsiness, dizziness and/or vertigo occur in 60 to 70% of patients, but rarely lead to drug withdrawal, although more troublesome effects, such as postural hypotension, ataxia, vision disturbance and toxic psychoses, may cause discontinuation of therapy. Thus, nabilone offers an effective alternative to the treatment options available in a difficult therapeutic area - those patients with severe gastrointestinal side effects from cancer chemotherapy who are refractory to conventional therapy.
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PMID:Nabilone. A preliminary review of its pharmacological properties and therapeutic use. 286 27

Acute, subchronic, and chronic studies were conducted in various species to evaluate and compare the toxicity of nabilone, a new synthetic 9-ketocannabinoid that is orally effective for the treatment of nausea and vomiting induced by cancer chemotherapy agents. The oral LD50 in mice and rats for nabilone formulated as a polyvinylpyrrolidone (PVP) codispersion was in excess of 1000 mg/kg. Among nonrodents, rhesus monkeys had a higher tolerance to the CNS depression induced by single oral doses of nabilone-PVP than did dogs. Rats fed dietary mixtures of nabilone-PVP which provided approximate daily nabilone doses of 1 to 93 mg/kg tolerated treatment for 3 months with no deaths. Treatment-related changes (at doses greater than or equal to 5 mg/kg) were limited to reduced body temperature, slight-to-moderate decreases in weight gain, and behavioral changes (e.g., hyperactivity, hyperirritability to touch, and hypoactivity). All dogs treated for 3 months with daily oral doses of up to 1.0 mg/kg survived; treatment-related effects were limited to transient episodes of ataxia and anorexia. Nabilone treatment of rats and dogs for 3 months produced no evidence of systemic toxicity in the clinical chemistry, hematology, or pathology parameters examined. Chronic treatment of dogs with daily oral doses of nabilone-PVP equal to 0.5, 1.0, or 2.0 mg of nabilone/kg produced cumulative toxicity; by the end of 7 months, 2, 6, and 7 dogs in the respective dose groups had died. In a number of instances, death was preceded by one or more convulsive episodes. In contrast to the dog, the toxic potential of nabilone was minimal in rhesus monkeys treated with nabilone-PVP for 1 year at daily oral nabilone doses of up to 2.0 mg/kg. The enzymatic reduction of the 9-keto group of nabilone to form carbinol metabolites was a major metabolic pathway for nabilone in dogs but not in rhesus monkeys. The carbinols were long-lived metabolites in the plasma of dogs and accumulated in the plasma compartment with time. Furthermore, the carbinol metabolites were found to concentrate in the brain tissues of treated dogs. Although the precise mechanism for this marked species difference in chronic toxicity is not known, the metabolic differences responsible for the presence of the carbinol metabolites at high concentrations in the plasma and brain over time may play a role in the toxicity observed in the dog.
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PMID:A species comparison of the toxicity of nabilone, a new synthetic cannabinoid. 288 99

The effects of two new cannabinoids, nabilone and canbisol, have been compared to delta 9-tetrahydrocannabinol (delta 9-THC) and chlordiazepoxide in behavioral tests in mice, rats, dogs and rhesus monkeys. Activity of mice was measured in a photocell device. Oral doses of 5 and 10 mg/kg of delta 9-THC and 200 mg/kg of chlordiazepoxide caused only a decrease in the initial high activity. Doses of 5 and 10 mg/kg of nabilone and 2.5, 5.0 and 10 mg/kg of canbisol decreased the initial high activity but increased the subsequent low activity. In rats delta 9-THC, nabilone and canbisol, but not chlordiazepoxide, slowed muricide and intracranial self-stimulation. Chlordiazepoxide, nabilone and canbisol, but not delta 9-THC, reduced reactivity of septal-lesioned rats. At ehe dosages studied only nabilone and canbisol reduced food consumption by rats. Ataxia in dogs was detected following as little as 0.062 mg/kg of delta 9-THC, 0.032 mg/kg of nabilone and 0.004 mg/kg of canbisol when given intravenously; orally, doses of more than 0.25 mg/kg of delta 9-THC, and 0.1 mg/kg of nabilone or canbisol were necessary. Rhesus monkeys working under multiple fixed-ratio fixed-interval schedules showed an increase in rate at some dose of all three cannabinoids but higher doses reduced responding, and responding was abolished following 3.0 mg/kg of delta 9-THC or nabilone or 0.3 mg/kg of canbisol. Chlordiazepoxide increased responding at all doses studied, 3.0 to 30.0 mg/kg. Nabilone and canbisol resemble chlordiazepoxide in som tests and delta 9-THC in other tests.
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PMID:Cannabinoids. I. Behavioral effects. 677 86