In vivo experimental approach to treatment against tabun poisoning

Figures & data

Figure 1.  Structures of oximes, pyridostigmine, and tabun.

Table 1.  Therapeutic effect of oximes and atropine administered as pretreatment or therapy in tabun-poisoned mice.

Dose of oxime	Pretreatment	Therapy	LD50 (µg/kg)	95% Confidence limits (µg/kg)	PI	MDP
5% LD50	K074 + atropine	None	898.5	678–1190	2.5	1.6
	K048 + atropine	None	1940.7	1479–2547	5.4	3.2
	TMB-4 + atropine	None	1425.1	1146–1772	4.0	2.0
	None^a	K074 + atropine	2016.5	1764–2304	6.4	5.0
	None	K048 + atropine	3686.4	3326–4085	11.6	10.0
	None	TMB-4 + atropine	2828.8	1939–4126	8.9	4.0
25% LD50	K074 + atropine	None	2264.1	1485–3453	6.4	3.2
	K048 + atropine	None	3595.0	1869–6913	10.1	3.2
	TMB-4 + atropine	None	5042.7	3457–7355	14.1	7.9
	None^a	K074 + atropine	2853.0	1227–6636	8.0	5.0
	None^b	K048 + atropine	2853.0	2428–3353	8.0	5.0
	None^b	TMB-4 + atropine	2542.0	1759–3672	7.1	5.0

^aReference 16.

^bReference 13.

Table 2.  Therapeutic effect of atropine and atropine plus oximes administered as pretreatment and therapy in tabun-poisoned mice.

Pretreatment	Therapy	LD50 (µg/kg)	95% Confidence limits (µg/kg)	PI	MDP
Atropine	None	485.3	381–617	1.4	1.0
Atropine	5% LD50 K074 + atropine	2137.0	1790–2548	6.0	4.0
Atropine	25% LD50 K074 + atropine	5661.0	4082–7850	15.9	15.9
Atropine	5% LD50 K048 + atropine	2853.0	2294–3547	8.0	4.0
Atropine	25% LD50 K048 + atropine	12,708.7	10,792–14,966	35.6	25.2
Atropine	5% LD50 TMB-4 + atropine	5996.5	5342–6731	16.8	12.6
Atropine	25% LD50 TMB-4 + atropine	9521.4	7980–11,360	26.7	20.0
5% LD50 K074 + atropine	5% LD50 K074 + atropine	1198.9	1004–1430	3.4	2.5
25% LD50 K074 + atropine	25% LD50 K074 + atropine	7131.8	5461–9313	20.0	16.0
5% LD50 K048 + atropine	5% LD50 K048 + atropine	4490.5	3115–6472	14.1	5.0
25% LD50 K048 + atropine	25% LD50 K048 + atropine	8002.0	6697–9560	25.2	20.0
5% LD50 TMB-4 + atropine	5% LD50 TMB-4 + atropine	5040.8	1999–12,708	16.0	10.0
25% LD50 TMB-4 + atropine	25% LD50 TMB-4 + atropine	12,702.8	8329–19,373	40.0	25.2

Table 3.  Therapeutic effect of pyridostigmine or pyridostigmine plus atropine administered as pretreatment in tabun-poisoned mice.

Pretreatment	Therapy	LD50 (µg/kg)	95% Confidence limits (µg/kg)	PI	MDP
5% LD50 pyridostigmine	None	611.0	480–778	1.7	1.3
25% LD50 pyridostigmine	None	400.3	—	1.1	1.0
5% LD50 pyridostigmine +atropine	None	1600.3	1154–2219	5.0	4.0
25% LD50 pyridostigmine +atropine	None	3982.0	3202–4952	12.5	6.3

Table 4.  Therapeutic effect of pretreatment with pyridostigmine and atropine followed by therapy with oximes and atropine in tabun-poisoned mice.

Pretreatment	Therapy	LD50 (µg/kg)	95% Confidence limits (µg/kg)	PI	MDP
5% LD50 pyridostigmine + atropine	5% LD50 K074 + atropine	3160.1	1643–6077	10.0	7.9
25% LD50 pyridostigmine + atropine	25% LD50 K074 + atropine	11,316.2	7852–16310	35.6	20.0
5% LD50 pyridostigmine + atropine	5% LD50 K048 + atropine	7564.8	6739–8492	23.8	20.0
25% LD50 pyridostigmine + atropine	25% LD50 K048 + atropine	11,989.5	10,049–14,305	37.8	25.2
5% LD50 pyridostigmine + atropine	5% LD50 TMB-4 + atropine	4490.6	3438–5864	14.1	7.9
25% LD50 pyridostigmine + atropine	25% LD50 TMB-4 + atropine	10,749.8	7049–16,395	33.9	20.0