The toxicological and pharmacological effects of furan analogs of muscarine.
The toxicological and pharmacological effects of furan analogs of muscarine.
复制标题
毒蕈碱呋喃类似物的毒理学和药理学作用。
DOI：
10.1016/s0041-008x(78)80033-7
复制
发表时间：
1978
影响因子：
3.8
通讯作者：
B. V. R. Sastry
中科院分区：
文献类型：
--
作者：
R. F. Ochillo;Arvind K. Chaturvedi;B. V. R. Sastry
呋喃毒碱类似物的毒理和药理作用奥奇罗，R.F.，Chaturvedi，A.K.，和Sastry，B.V.R.(1978)Toxicol。APPL药业，43，73-83。呋喃甲基三甲基碘化铵(Furmetide，FT)、5-甲基呋喃(5-MFT)、5-羟甲基呋喃(5-HMFT)、5-氯甲基呋喃(5-CMFT)、5-甲氧基呋喃(5-MOFT)、四氢呋喃(THFT)和5-甲基三甲基碘化铵(5-MTTA)是与毒蛾碱结构相关的化合物。这些化合物对小鼠的毒性按以下顺序递减：5-MTTA>；5-MOFT>；THFT>；5-MFT>；FT>；5-HMFT>；5-cmft。这些化合物的呋喃氧周围的电子密度也以相同的顺序减少。这些动物在注射致死剂量后5分钟内死亡。这些化合物对胆碱乙酰转移酶和胆碱酯酶无明显抑制作用。小鼠的毒性症状包括过度流口水、流泪、排尿和排便。所有的外周副交感神经体征都被阿托品消除，这表明这些体征是通过副交感神经系统调节的。然而，阿托品、六甲基溴铵和d-管胡萝卜碱并不改变半数致死量。死亡原因似乎是呼吸抑制和/或窒息。当动物在注射致死剂量后的最初5分钟内通过人工呼吸维持时，它们无限期存活。死亡的原因可能是大量释放乙酰胆碱，并通过直接释放乙酰胆碱或呋喃类似物阻断参与维持呼吸的多个胆碱能突触。
The Toxicological and Pharmacological Effects of Furan Analogs of Muscarine. Ochillo, R. F., Chaturvedi, A. K., and Sastry, B. V. R. (1978) Toxicol. Appl. Pharmacol.43, 73–83. Furfuryltrimethylammonium iodide (Furmethide, FT), 5-methylfurmethide (5-MFT), 5-hydroxymethylfurmethide (5-HMFT), 5-chloromethylfurmethide (5-CMFT), 5-methoxyfurmethide (5-MOFT), tetrahydrofurmethide (THFT), and 5-methylthenyltrimethylammonium iodide (5-MTTA) are structurally related to muscarine. The toxicities of these compounds in mice decrease in the following order: 5-MTTA>5-MOFT>THFT>5-MFT>FT>5-HMFT >5-CMFT. The electron densities around the furan oxygen of these compounds decrease in the same order. The animals died within 5 min after administration of the lethal dose. These compounds did not significantly inhibit choline acetyltransferase and cholinesterase. Signs of toxicity in mice included excessive salivation, lacrimation, urination, and defecation. All peripheral parasympathetic signs were abolished by atropine, suggesting that these were mediated through the parasympathetic nervous system. However, atropine, hexamethonium, and d-tubocurarine did not alter the LD50. Death appeared to be due to respiratory depression and/or asphyxia. The animals survived indefinitely when they were maintained by artificial respiration during the initial 5 min after administration of lethal doses. The cause of death may possibly be due to bulk release of acetylcholine and blockade at multiple cholinergic synapses involved in the maintenance of respiration by released acetylcholine or furan analogs directly.