Fechter L D, Richard C L, Mungekar M, Gomez J, Strathern D
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene, Maryland 21205.
Fundam Appl Toxicol. 1989 Jan;12(1):56-61. doi: 10.1016/0272-0590(89)90061-4.
Butyl nitrite is the predominant and presumed active ingredient in a variety of commercial preparations sold as "room odorizers." These compounds have significant abuse potential, giving the user the sensation of a "rush", which may be related to their intense cardiovascular effects. The pharmacological properties of butyl nitrites are similar to those of amyl nitrite which is also abused for its psychological effects, but whose availability is limited by prescription for treatment of angina. A significant body of literature suggests that the inner ear is vulnerable to acute hypoxic exposure. Since butyl nitrite induces high levels of methemoglobin and also reduces blood pressure due to peripheral vasodilation, we hypothesized that this compound might produce auditory dysfunction. We studied the effect of acute exposure to a butyl nitrite "room odorizer" on 10- and 40-kHz auditory function in rats. A loss in auditory sensitivity was found at both frequencies on the day following administration of the compound. Auditory dysfunction tended to subside over the next several days at 40 kHz, although a significant loss of sensitivity for tones of 10 kHz was observed over a 6-day period after administration of the agent. Methemoglobin levels measured in rats of the same age were elevated significantly 30 and 60 min after butyl nitrite to levels of 30-45%. Methemoglobin levels were found to be normal 18 hr after administration when the first audiometric tests were conducted. The data suggest that auditory function in the middle of the rats' auditory range, 10 kHz, was disrupted for a longer period than was high-frequency (40 kHz) auditory function.
亚硝酸丁酯是多种作为“室内除臭剂”出售的商业制剂中的主要成分,也是被认为具有活性的成分。这些化合物具有很大的滥用潜力,会给使用者带来“快感”,这可能与其强烈的心血管效应有关。亚硝酸丁酯的药理特性与亚硝酸异戊酯相似,后者也因其心理效应而被滥用,但其可用性因用于治疗心绞痛的处方而受到限制。大量文献表明,内耳易受急性缺氧暴露的影响。由于亚硝酸丁酯会诱导高水平的高铁血红蛋白,并且还会因外周血管扩张而降低血压,我们推测这种化合物可能会导致听觉功能障碍。我们研究了急性暴露于亚硝酸丁酯“室内除臭剂”对大鼠10千赫和40千赫听觉功能的影响。在给予该化合物后的当天,两个频率的听觉敏感性均有所下降。40千赫时,听觉功能障碍在接下来的几天里趋于消退,尽管在给予该药剂后的6天内,10千赫音调的敏感性仍有显著下降。在同年龄大鼠中测量的高铁血红蛋白水平在亚硝酸丁酯给药后30分钟和60分钟显著升高至30% - 45%。在进行首次听力测试时,给药18小时后高铁血红蛋白水平恢复正常。数据表明,大鼠听觉范围中间频率10千赫的听觉功能比高频(40千赫)听觉功能受到干扰的时间更长。