Table 2.

Inhibition of [³H]MK-801 and [³H]ifenprodil binding to rat cortical membranes by pentamidine analogs with piperazine and homopiperazine bridge (including open-chain isosters)

	R	R′	[3H]MK-801			[3H]ifenprodil
			IC50 ± SD (n) (µM)		Ratio	IC50 ± SD (n)
			No spm	30 µM spm		No spm
16	H	—	3.08 ± 0.59 (4)	70.7 (2)	26.2 (2)	17.0 (2)
17	i-Pr	—	21.4 ± 5.2 (4)	544 ± 34 (3)	32.9 ± 5.8 (3)	n.d.
18	c-Pr	—	19.4 ± 7.4 (4)	466 (2)	21.8 (2)	n.d.
19	n-Pr	—	15.9 ± 4.9 (4)	371 (2)	21.8 (2)	n.d.
20	n-Bu	—	10.3 ± 3.6 (5)	139 ± 32 (4)	16.0 ± 3.2 (4)	n.d.
21	c-Pent	—	9.25 ± 3.85 (5)	159 ± 59 (4)	19.3 ± 6.4 (4)	n.d.
22	(CH2)2	—	6.43 ± 1.64 (4)	106 ± 20 (3)	15.1 ± 4.1 (3)	n.d.
23	(CH2)3	—	23.8 ± 8.9 (5)	264 ± 26 (3)	13.6 ± 5.2 (3)	n.d.
24	H	—	0.25 ± 0.07 (14)	5.47 ± 1.42 (6)	20.4 ± 7.3 (6)	19.1 (2)
25	i-Pr	—	17.7 ± 4.8 (4)	389 ± 85 (3)	25.3 ± 10.5 (3)	n.d.
26	c-Pr	—	11.2 ± 2.9 (4)	212 ± 32 (4)	19.9 ± 5.7 (4)	n.d.
27	t-Bu	—	34.6 ± 4.1 (3)	562 (2)	16.8 (2)	n.d.
28	n-Bu	—	9.94 ± 3.72 (3)	103 ± 3 (3)	11.2 ± 3.3 (3)	n.d.
29	c-Pent	—	8.13 ± 0.29 (3)	85.7 ± 7.8 (3)	10.6 ± 1.2 (3)	n.d.
30	2-HO-Et	—	9.44 ± 2.70 (6)	324 ± 34 (5)	35.7 ± 6.9 (5)	n.d.
31	3-HO-Pr	—	41.2 ± 13.2 (4)	427 (2)	9.72 (2)	n.d.
32	(CH2)2	—	3.03 ± 0.21 (3)	92.2 (2)	30.1 (2)	n.d.
33	(CH2)3	—	12.8 ± 4.3 (3)	143 ± 15 (3)	11.7 ± 2.5 (3)	n.d.
34	H	H	2.01 ± 0.76 (6)	50.7 ± 13.8 (5)	30.2 ± 10.4 (5)	0.76 ± 0.05 (3)
35	Me	H	3.18 ± 0.60 (3)	85.3 (2)	30.2 (2)	7.14 (2)
36	Et	H	2.61 ± 0.55 (4)	48.1 ± 6.5 (3)	19.3 ± 7.8 (3)	13.0 (2)
37	Me	Me	2.71 ± 0.41 (3)	54.5 (2)	20.9 (2)	16.9 (2)
38	Et	Et	1.14 ± 0.19 (3)	13.8 (2)	11.8 (2)	9.16 (2)
39	H	H	10.0 ± 2.3 (3)	148 (2)	17.0 (2)	77.7 (2)
40	Me	Me	1.84 ± 0.65 (4)	24.7 ± 0.8 (3)	14.7 ± 5.3 (3)	31.2 (2)

Definitions as in caption to Table 1;

c-pent, cyclopentyl.