Disease relevance of l-Nantradol

• There is substantial clinical evidence that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and its synthetic analogs (nabilone and levonantradol) can prevent emesis in cancer patients receiving chemotherapy [1].
• The cannabinoid agonist levonantradol dose-dependently decreased general and locomotor activity and increased bradykinesia [2].
• A phase II double-blind placebo-controlled, randomized dose-ranging trial was undertaken to determine the antiemetic efficacy and toxicity of the synthetic cannabinoid levonantradol at doses of 0.5, 1.0, 1.5, and 2.0 mg [3].
• Evaluation of intramuscular levonantradol and placebo in acute postoperative pain [4].
• Levonantradol did not affect the incidence or extent of artificial melanotic lung metastases, nor did it modify lymphoreticular cell stimulation [5].

Psychiatry related information on l-Nantradol

• Behavioral experiments demonstrated that the cannabinoid agonist levonantradol inhibits both newt spontaneous locomotor activity and courtship clasping behavior [6].

High impact information on l-Nantradol

• Alone, the CB(1) cannabinoid receptor agonist levonantradol (0.01-0. 3 mg/kg) induced sedation, ptosis, and decreased locomotor and general activity [7].
• To investigate whether dopamine agonists attenuate the sedative effects of a cannabinoid agonist in monkeys, we compared the effects of D(1) or D(2) dopamine receptor agonists on spontaneous behavior in three to six cynomolgus monkeys (Macaca fasicularis) alone and after administration of a low dose of the CB(1) agonist levonantradol [7].
• Effects of single and repeated daily injections of morphine, clonidine and l-nantradol on responding of squirrel monkeys under escape titration [8].
• Electric shock titration in squirrel monkeys following administration of nantradol, levonantradol, or N-methyl levonantradol [9].
• Dose ranging evaluation of the antiemetic efficacy and toxicity of intramuscular levonantradol in cancer subjects with chemotherapy-induced emesis [3].

Chemical compound and disease context of l-Nantradol

• In rhesus monkeys, acute administration of levonantradol and nantradol produced signs of CNS depression, including ataxia with body sag, pupil dilation, ptosis, dozing, and reduced responsivity to external stimuli [10].
• The most common side effect of levonantradol were somnolence, dry mouth, dizziness, tachycardia, postural hypotension, and blurred vision, while those for prochlorperazine were somnolence, dry mouth, and tachycardia [11].

Biological context of l-Nantradol

• Pharmacokinetics of levonantradol in laboratory animals and man [12].
• The current phase I trial was undertaken to determine: 1) the maximally tolerated dose; 2) the side effects at the different dosage levels; and 3) to evaluate the antiemetic efficacy of levonantradol in patients receiving emesis-producing chemotherapy [13].

Anatomical context of l-Nantradol

• Levonantradol enhanced binding of 3H-diazepam to rat cortical membranes [14].
• Levonantradol (0.3 mg/kg subcutaneously) decreases the tRACh in the hippocampus and striatum by 53 and 30 per cent, respectively [15].

Associations of l-Nantradol with other chemical compounds

• Twenty cancer patients who received chemotherapy were entered into a double-blind crossover design antiemetic study comparing 1 mg levonantradol, an investigational synthetic cannabinoid, to 10 mg prochlorperazine [11].
• This report describes a striking structural homology between PGE1 and levonantradol as elucidated by x-ray and conformational studies [16].
• The effects of morphine, levonantradol, and N-methyllevonantradol administered to squirrel monkeys by intramuscular injection were examined on an electric shock discrimination test [17].
• In a randomized crossover study 57 cancer patients receiving chemotherapy with high emetic potential were treated with low-dose levonantradol or standard-dose metoclopramide and crossed over to the other antiemetic drug in the next identical chemotherapy cycle [18].
• A pilot study and randomised trial compared the anti-emetic effect of a standard drug (Chlorpromazine 26 mg) with Levonantradol at two doses (0.5 and 0.75 mg) in patients receiving palliative single fraction radiotherapy to sites likely to cause nausea and vomiting [19].

Gene context of l-Nantradol

• Levonantradol, a synthetic cannabinoid analog, also increased adenylate cyclase activity while its optical isomer dextronantradol did not [20].
• While no totally noncannabimimetic agents with potent analgesic effects have yet been identified among derivatives of THC, selectivity has been uncovered for levonantradol, HHC (racemic-9-nor, 9-beta-OH-hexahydrocannabinol) and several structurally related compounds [21].

Analytical, diagnostic and therapeutic context of l-Nantradol

• We have recently described a potent, cannabinoid-related analgetic, levonantradol, which acts stereospecifically in animals to produce analgesia qualitatively similar to morphine but at 1/9 to 1/34 the dose [16].
• We report here our initial observations with the antiemetic levonantradol in 12 patients with advanced solid tumors receiving cytotoxic polychemotherapy [22].
• The pharmacokinetic behavior of levonantradol, administered orally or intramuscularly, has been investigated in man at dose levels of 0.25 to 3.0 mg and in animals at 0.03 to 10 mg/kg, using a specific HPLC/electrochemical assay [12].
• Levonantradol for chemotherapy-induced emesis: phase I-II oral administration [23].

References