Disease relevance of NSC7761

• Chronic treatment of rodents with 2,4-dithiobiuret (DTB) induces a neuromuscular syndrome of flaccid muscle weakness that mimics signs seen in several human neuromuscular disorders such as congenital myasthenic syndromes, botulism, and neuroaxonal dystrophy [1].
• Daily dosing with 1-3 mg/kg dithiobiuret for 4-5 days causes progressive, generalised muscle weakness which is fatal in about 50% of cases on day 4 or 5 [2].
• Potential neuromuscular toxicity of 2,4-dithiobiuret in the rat [3].
• Increasing the daily dose of dithiobiuret (DTB) given to rats from 0.5 to 1 to 5 mg/kg shortened the latency to onset of treadmill failure and associated flaccid muscle tone from 7 to 5 to 3 days, respectively [4].
• Effects of the paralytic agent 2,4-dithiobiuret on viability and morphology of rat pheochromocytoma (PC12) cells [5].

High impact information on NSC7761

• Impairment of synaptic vesicle exocytosis and recycling during neuromuscular weakness produced in mice by 2,4-dithiobiuret [1].
• Voltage clamp analysis reveals multiple populations of quanta released at neuromuscular junctions of rats treated with 2,4-dithiobiuret [6].
• Daily treatment of rats with 2,4-dithiobiuret (DTB, 1 mg/kg/day i.p.) produces a flaccid neuromuscular weakness first observed in the hindlimbs after 5 to 6 days of treatment [7].
• Treatment of rats for 5 to 6 days with dithiobiuret (DTB, 1 mg/kg/day, ip) causes a flaccid, ascending neuromuscular weakness which is associated with a decreased end-plate potential (EPP) amplitude, quantal content, miniature end-plate potential (MEPP) frequency, and prolongation of MEPP and EPP rise and decay times [8].
• To evaluate the hypothesis that depressed neuromuscular transmission causes dithiobiuret (DTB)-induced muscle weakness in rats, the temporal development of impaired treadmill performance and deficits in the nerve-elicited muscle contractions were compared during daily treatment with the toxicant (DTB, 1 mg/kg/day X 6 days) [9].

Chemical compound and disease context of NSC7761

• Studies were conducted using harmaline, a tremorigen; scopolamine; methyl scopolamine; and 2,4-dithiobiuret (DTB), a compound that causes muscle weakness by interfering with cholinergic transmission at the neuromuscular junction [10].

Biological context of NSC7761

• Effects of dose and dosing regimen on tissue distribution and elimination kinetics of [14C] dithiobiuret in rats [11].

Anatomical context of NSC7761

• Effects of dithiobiuret intoxication on motor end plates in sternocostalis and hindlimb muscles of female rats [2].
• Weanling, juvenile and adult rats both sexes were treated with 1 mg/kg/day [14C] dithiobiuret (DTB) until they developed skeletal muscle weakness as detected by failure in a rotarod test [12].

Associations of NSC7761 with other chemical compounds

• 2,4-Dithiobiuret was given i.p. to rats for 4 days at a daily dosage of 1 mg/kg and the development of the lesion associated with neuromuscular dysfunction studied in hindlimb lumbrical muscles [13].

Analytical, diagnostic and therapeutic context of NSC7761

• Daily administration of dithiobiuret (DTB, 1 mg/kg X 6 days, ip) produced delayed onset muscle weakness in rats as indicated by failure in a treadmill test [14].

References