9H-Thioxanthen-9-one, 1-((2-(diethylamino)ethyl)amino)-4-(hydroxymethyl)-, methanesulfonate (1:1)

Interactions of caffeine with chemicals known for their effects on chromosomal segregation during meiosis of Saccharomyces cerevisiae were studied. It appears that caffeine does interfere with the action of other compounds during the different phases of meiosis. Treatments with methyl methanesulphonate (MMS) and cadmium chloride (CdCl2) resulted in a synergistic effect consisting of an increase in the frequency of recombination. The greatest effects were found on the induction of diploid spores: MMS, hycanthone, and distamycin demonstrated strong, benlate little synergistic action. ...Concerning disomic induction: caffeine reduced (or left unchanged) the effect on non-disjunction when MMS and hycanthone were used. /Salt not specified/

/HUMAN EXPOSURE STUDIES/ Two of 8 patients treated with a single im injection of 3 mg/kg bw hycanthone for Schistosoma haematobium infestation developed severe hepatocellular injury, with the histological pattern of acute toxic hepatitis.

/SIGNS AND SYMPTOMS/ Symptoms of exposure to this compound include nausea, vomiting, abdominal discomfort, headache, dizziness, myalgia, anorexia and, rarely, transient and minimal ECG changes, acute hepatic necrosis and death. Other symptoms include weakness, diarrhea and weight loss. Hepatotoxicity occurs. Exposure can cause acute toxic hepatitis, vertigo, fall in blood pressure, giddiness and liver damage (sometimes severe). There have been cases of psychotic disturbance, acute pancreatitis, icterus and cirrhosis. It may also cause hallucinations and muscle weakness.

/SPECIAL STUDIES/ No chromosome abnormalities were observed in lymphocytes from patients treated with a single injection of 2.5 mg/kg bw hycanthone.

Hycanthone mesylate

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 13: (1977) Some Miscellaneous Pharmaceutical Substances

1987

1987

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Three groups of 144, 59, and 103 female Swiss-Webster CD1 mice were infected by tail immersion with 16 S. mansoni cercariae; 8, 12, and 16 weeks after infection they were given three im injections of 0, 3, or 60 mg/kg bw hycanthone. Of 101, 38, and 74 mice in the three groups that survived 60 or more weeks, 0, 1, and 9 (12.2%) developed hepatocellular carcinomas. The increased incidence at the higher dose level was reported to be statistically significant (P=0.001).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Experiments were designed to determine whether hycanthone methanesulfonate (1-((2-(diethylamino)ethyl)amino)-4-(hydroxymethyl)thioxanthen-9-one monomethanesulfonate), an antischistosomal drug, and its analog, IA-4-N-oxide (8-chloro-2-(2-(diethylamino)ethyl)-2H-(1)benzothiopyrano(4,3,2-cd)indazole 5-methanol monomethanesulfonate), will induce neoplastic lesions in the livers of mice not infected with Schistosoma mansoni. All the mice received a single i.m. injection of hycanthone methanesulfonate (76 mg/kg), IA-4-N-oxide (80 mg/kg), or an equivalent volume of the solvent, 0.9% NaCl solution, 42 hr after partial hepatectomy. Of the mice receiving hycanthone methanesulfonate and living 200 days or longer, hepatocellular carcinoma was seen in 11.5% and liver sarcoma was seen in 4.2%. This type of malignant neoplasm was not seen in the animals receiving either IA-4-N-oxide or 0.9% NaCl solution. In addition, mice receiving hycanthone methanesulfonate showed a significantly higher incidence of both type 1 (43% compared to 21% in controls) and type 2 (21% compared to 12% in controls) hepatocyte neoplasms. Mice receiving IA-4-N-oxide showed no increased incidence of neoplasms.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In mice, single im doses of 35 or 50 mg/kg bw hycanthone mesylate administered on day 7 of gestation caused malformations in more than 73% of the litters. In rabbits, hycanthone mesylate showed embryolethal and teratogenic effects at an im dose of 50 mg/kg bw on days 7, 8, and 9 of gestation. The most frequent malformations were exencephaly, hydrocephaly, microphthalmia and abnormalities of the axial skeleton.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Effects of hycanthone were studied in maturing and primordial oocytes and in male germ cells throughout spermatogenesis. No induction of dominant lethality was observed for treated males while a significant increase in embryonic death, expressed around the time of implantation, was observed in females that mated within 4.5 days after treatment. These effects were the result of dominant lethal mutations induced in maturing oocytes and not of maternal toxicity as indicated by the presence of chromosomal aberrations observed at first-cleavage metaphase of zygotes obtained from treated females. These results add support to the hypothesis that certain intercalating chemicals, which are not mutagenic to male mice, may be mutagenic to females... .

For more Non-Human Toxicity Excerpts (Complete) data for HYCANTHONE MESYLATE (11 total), please visit the HSDB record page.

SKIN CONTACT: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Respirator Recommendation.

EYE CONTACT: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, ... IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital.

LD50 Rat oral 980 mg/kg /Hycanthone/

LD50 Rat sc 286 mg/kg /Hycanthone/

LD50 Rat iv 75 mg/kg /Hycanthone/

LD50 Mouse oral 1120 mg/kg /Hycanthone/

For more Non-Human Toxicity Values (Complete) data for HYCANTHONE MESYLATE (12 total), please visit the HSDB record page.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).