Evaluation of the Therapeutic Efficacy of some Antimuscarinics against Soman in Vivo

✍ Scribed by Wai-Man Lau; Katie J. Lewis; Raymond M. Dawson

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 734 KB
• Volume: 16
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/(sici)1099-1263(199609)16:5<423::aid-jat367>3.0.co;2-z

✦ Synopsis

The therapeutic efficacy of tacrine, atropine and glycopyrrolate alone or in combination with the oxime HI-6 against soman was evaluated in anaesthetized rats. Arterial blood pressure, heart rate, respiratory frequency and body temperature were monitored in vivo. Blood cholinesterases were determined after each drug or soman challenge. At the lowest concentration tested (2.5mg kg-I), tacrine was effective in improving the survivability of the rat by a factor of 2.6 (protection ratio), whereas the protection by atropine or glycopyrrolate was either insignificant or only marginally effective (protection ratio ranged from 1.0 to 1.9). In combination with HI-6, atropine increased the ratio to 4.6. In contrast, tacrine with HI-6 failed to improve the efficacy of the regimen, while glcopyrrolate plus HI-6 showed only slight improvement.

The four physiological parameters monitored were relatively constant during the time course of the experiment in both the control and those with drug therapy. The more noticeable changes occurred toward the end of the experiment when sufficient amount of soman was injected to cause lethality. Death of the animal was usually preceded by a surge of arterial blood pressure and heart rate and a decrease in respiratory frequency. These physiological parameters rapidly deteriorated to zero just before the animal died. Blood and plasma cholinesterases were significantly inhibited after the animal received a relatively small dose of soman (20 Fg kg-I) and were almost completely inactivated after the lethal dose of soman was administered. However, these changes of enzyme activity did not correspond well with the survivability of the rat. The inclusion of HI-6 with the three antimuscarinics appeared to be capable of protecting some cholinesterases against soman.