Therapeutic Efficacy of HI-6 in Soman Poisoned Marmoset Monkeys (GeslaagdeBehandeling van Marmoset Apen met het Oxim HI-6 na Somanvergiftiging)

摘要

The therapeutic efficacy of the oxime HI-6 was tested in marmoset monkeyspoisoned with the irreversible cholinesterase inhibitor soman. Male marmosets were poisoned with 5 x LD50 soman (i.m.), treated immediately with diazepam (0.2 mg/kg i.v.) and 15 sec later with atropine (0.5 mg/kg i.m.) and either HI-6 (50 mg/kg i.m.) or saline. Five out of 6 HI-6 treated animals survived more than 24 h, one of these died after 4 days. In the first 2 h after soman, the blood ChE activity remained about 5% of control value. HI-6 achieved its plasma peak 5 min after injection and then dropped with an elimination t1/2 of about 45 min. The 3 saline treated marmosets died within 8 min after soman with a blood ChE activity of <4%. Another group of marmosets was treated identically as described except that 3 saline treated animals were sacrified at 5 min after soman and 3 HI-6 treated animals at 10 min. The blood AChE activity in saline treated animals dropped to 0-1% within 2 min, and in HI-6 treated animals to 0.4-2.7%. The neuromuscular transmission (NMT) in diaphragms from HI-6 treated animals was about 30% higher than that in controls. Administration in vitro of HI-6 (1.5 mM) resulted in about 20% reversible improvement of NMT in both groups attributed to pharmacological effects of the oxime. Subsequent administration of soman (0.2 micromoles) led to a decrease of NMT only in diaphragms from HI-6 treated monkeys, indicating that in vivo reactivation or protection of AChE had occurred. However, biochemically the AChE activities in diaphragms (about 3%) and brains (about 0.5%) did not differ significantly between saline and HI-6 treated animals, mainly due to unbound soman that inhibited AChE upon homogenization.