Table 1

Effect of in vitro application of newly synthesized CPP derivatives on gCl and evaluation of their effect on heterologously expressed CLC channels

		Effect on CLC Channels Expressed in Oocytes
Compound	Effect on Muscle gCl	CLC-1	D9	ΔNCLC-2	CLC-5	CLC-Kb(c)
	% reduction
CPA (N1)		–	–	–	–	N.D.
CPP (N2)	58 ± 13^1-150	–	N.D.	–	–	N.D.
CPV (N3)		–	N.D.	–	–	N.D.
CPPA (N4)		–	–	–	–	N.D.
N5	16 ± 6^1-150	–	–	–	–	N.D.
N6	4 ± 6	N.D.	N.D.	N.D.	–	N.D.
N7	57 ± 10^1-150	N.D.	N.D.	N.D.	–	N.D.
N8	15 ± 6^1-150	N.D.	N.D.	N.D.	N.D.	N.D.
N9	2 ± 7	N.D.	–	N.D.	N.D.	N.D.
N10	0 ± 7	N.D.	N.D.	N.D.	N.D.	N.D.
N11	13 ± 7^1-150	–	^1-213	–	–	N.D.
N12	25 ± 8^1-150		^1-213	N.D.	N.D.	N.D.
N13	46 ± 10^1-150	–	^1-213	–	–	^1-213
N14	33 ± 8^1-150	–	^1-213	N.D.	–	N.D.
N15	32 ± 8^1-150	–	^1-213	N.D.	–	N.D.
N16	48 ± 9^1-150	–	–	N.D.	N.D.	N.D.

For the evaluation on heterologously expressed channels currents were measured using two-electrode voltage clamp as described under Materials and Methods; substances were applied at 200 μM. At least three oocytes were measured for each tested substance. For CLC-1 and D9, only the “short-term” effects are evaluated in the Table (i.e. effects after a brief incubation of <30 s). After a longer incubation time, significant effects were observed for CLC-1 for the strict derivatives of CPP (compounds N2 to N4) (Pusch et al., 2000). For CLC-5 and Δ NCLC-2, the effects were evaluated after about 5 to 10 min of incubation.

↵1-150 Significantly different with respect to the control value obtained in the absence of drug (P < 0.05).
↵1-213 , Tested and effective (for details in these cases, see text).
–, Tested and no or only slight effect (less than 30% block).
N.D., not determined.