Table 1

Binding characteristics, FAAH inhibition, and pharmacological activity after i.v., i.t., and i.c.v. administration of the methylfluorophosphonate analogs

Analog	N^1-a	KD^1-b	FAAH^1-c	S.A.^1-d	R.T.^1-d	% MPE^1-d	% MPE^1-e	% MPE^1-f
O-1625	20∶2	2.9 ± 0.3	55 ± 8	14 (5–36)	13 (6–26)	N.D.^1-g	111 (28–445)	190 (40–890)
	n-6	(75)		(70)	(−4.4)	(1)	(73)	(67)
O-1626	20∶1	17 ± 2.4	103 ± 7	N.D.^1-g	53 (38–75)	N.D.^1-g	68 (17–268)	75 (28–204)
	n-6	(70)		(38)	(−2.5)	(2)	(72)	(90)
O-1624	20∶0	795 ± 72	137 ± 22	26 (11–64)	N.D.^1-g	N.D.^1-g	N.D.^1-g	N.D.^1-g
		(60)		(54)	(−1.3)	(7)	(17)	(15)
O-1623	18∶0	9.7 ± 1.5	48 ± 13	N.D.^1-g	41 (13–120)	N.D.^1-g	N.D.^1-g	N.D.^1-g
		(58)		(48)	(−3.0)	(10)	(56)	(30)
O-1705	16∶0	N.D.	78 ± 12	18 (11–30)	10 (8–12)	15 (9–25)	N.D.^1-g	N.D.^1-g
		(58)		(60)	(−6.2)	(68)	(45)	(45)
O-1778	12∶0	2.5 ± 0.3	3.0 ± 0.2	0.6 (0.2–1.5)	3.2 (2.6–4.1)	2.2 (1.5–3.3)	2.2 (1.5–3.3)	20 (9–43)
		(75)		(90)	(−6.7)	(100)	(100)	(84)
O-1887	8∶0	>10,000	15 ± 3	0.6 (0.5–0.7)	1.0 (0.8–1.2)	0.5 (0.5–0.6)	7.7 (2.9–21)	11 (4.8–27)
				(90)	(−3.8)	(100)	(91)	(93)

↵1-a Carbon length of the alkyl moiety∶number of unsaturated bonds; n designates position of double bond from terminal carbon.
↵1-b Results (nM) presented as means ± S.E. with maximal displacement provided below in parentheses.
↵1-c Expressed as IC₅₀ values in nanomolar.
↵1-d Spontaneous activity (S.A.), rectal temperature (R.T.), and tail-flick response (% MPE) are expressed as ED₅₀ values (mg/kg) followed by confidence limits in parentheses after i.v. administration. Below the ED₅₀ values are the maximal effects produced.
↵1-e Antinociceptive activity in the tail-flick procedure after i.t. administration. ED₅₀ (CL) expressed as micrograms per mouse with the maximal effect at doses up to 400 μg/mouse in parentheses.
↵1-f Antinociceptive activity in the tail-flick procedure after i.c.v. administration. ED₅₀ (CL) expressed as micrograms per mouse.
↵1-g N.D., could not be determined.