A comparison of the reactivating and therapeutic efficacy of newly developed bispyridinium oximes (K250, K251) with commonly used oximes against tabun in rats and mice

Figures & data

Figure 1.  Chemical structure of oximes.

Table 1.  LD₅₀ values of oximes following i.m. administration in rats and mice.

OXIMES	LD50 (mg/kg) ± 95% confidence limit
	Rats	Mice
Obidoxime	211.1 (176.4 – 252.6)	188.4 (156.3 – 208.0)
HI-6	781.3 (738.4 – 826.6)	671.3 (627.4 – 718.3)
Trimedoxime	150.5 (142.1 – 159.4)	149.3 (124.1 – 184.5)
K250	> 800	555.6 (475.8 – 648.8)
K251	358.2 (293.6 – 429.8)	116.1 (105.1 – 128.1)

Table 2.  Percent reactivation of tabun-inhibited AChE by oximes in rat blood, diaphragm and brain in vivo.

TREATMENT	AChE activity (μkat/L or μkat/kg)
	Blood	Diaphragm	Brain
Atropine	3.78 ± 0.22^a	2.49 ± 0.94^a	6.33 ± 1.48^a
Atropine + obidoxime(% reactivation^b)	4.88 ± 0.24(12.2^*x)	4.37 ± 0.65(16.0^*x)	15.34 ± 1.84(8.3^*x )
Atropine + HI-6(% reactivation)	3.49 ± 0.16(0)	1.81 ± 0.44(0)	9.29 ± 0.97(2.3)
Atropine + trimedoxime(% reactivation)	3.99 ± 0.22(2.4)	5.41 ± 1.15(24.8^*x)	19.14 ± 2.54(11.7^*x)
Atropine + K250(% reactivation)	3.51 ± 0.09(0)	2.33 ± 0.79(0)	6.84 ± 1.53(0.5)
Atropine + K251(% reactivation)	3.97 ± 0.18(2.2)	2.54 ± 1.07(0.5)	8.61 ± 1.56(2.1)

^a Means ± S.D., N = 8. The untreated control value (saline control) for rat blood AChE activity was 12.48 (μkat/L), for diaphragm AChE activity 14.25 μkat/kg and for brain AChE activity 115.6 μkat/kg.

^b Percent reactivation was determined using the AChE activity values: {1- [((saline control) – (oxime + atropine))/((saline control) – (atropine control))]} × 100.

^* Significantly different from the atropine group at a level of P < 0.05, ^x significantly different from the atropine + HI-6 (K250, K251) group at a level of P < 0.05 as determined by the Student’s test.

Table 3.  The influence of the type of oxime on the potency of antidotal treatment to eliminate acute lethal effects of tabun in mice.

Treatment	LD50 (μg/kg) ± 95% confidence limit	Protective ratio
-----	295.2 (275.5 – 317.9)	----
Obidoxime + atropine	454.2 (395.2 – 510.2)^*	1.54
HI-6 + atropine	334.4 (281.6 – 397.1)	1.13
Trimedoxime + atropine	524.5 (500.5 – 549.6)^*x	1.78
K250 + atropine	367.0 (331.2 – 431.2)^*	1.24
K251 + atropine	389.4 (319.1 – 476.4)^*	1.32

^* significantly different from the untreated group at the level of P < 0.05, ^x significantly different from the group treated by atropine in combination with HI-6 (K250, K251) at the level of P < 0.05.