Pharmacological Properties of DOV 315,090, an ocinaplon metabolite

BMC Pharmacology

Table 2 Properties of diazepam, ocinaplon and DOV315090 determined by two-electrode voltage clamp electrophysiology using Xenopus oocytes injected with cRNA.

Receptor Type		α₁β₂γ_2S	α₂β₂γ_2S	α₃β₂γ_2S	α₅β₂γ_2S
diazepam (DZ)	EC₅₀ (μM)	0.04 (8)	0.03 (10)	0.092 (5)	0.025 (5)
	pEC₅₀	7.46 ± 0.07	7.60 ± 0.044	7.04 ± 0.05	7.51 ± 0.11
	E_max, %	144 ± 8.0	157 ± 14	232 ± 31	224 ± 24
ocinaplon (OC)	EC₅₀ (μM)	2.93 (4)	9.12 (5)	8.01 (4)	3.5 (4)
	pEC₅₀	5.57 ± 0.11	5.04 ± 0.03	5.16 ± 0.14	5.48 ± 0.07
	EC₅₀/DZ EC₅₀	77	350	87	139
	E_max, %	132 ± 8	150 ± 6	181 ± 18	84 ± 4
	E_max/DZ E_max	0.91	0.95	0.78	0.37
DOV315090 (MET)	EC₅₀ (μM)	4.87 (4)	12.5 (4)	10.21 (4)	10.14 (4)
	pEC₅₀	6.32 ± 0.05	4.92 ± 0.09	5.00 ± 0.05	5.03 ± 0.10
	EC₅₀/DZ EC₅₀	128	482	111	405
	EC₅₀/OC EC₅₀	1.66	1.37	1.27	2.92
	E_max, %	192 ± 4	139 ± 23 *	340 ± 35 *	68 ± 8
	E_max/DZ E_max	1.33	0.88	1.46	0.30
	E_max/OC E_max	1.45	0.92	1.87	0.81

Drugs were prepared from DMSO stock solution prior to experiment, EC₁₀s of GABA were used, errors are SEM of fitted parameter values from the number of oocytes given in parentheses. Results from each oocyte were fitted independently and fitted parameters were averaged to calculate means and SEM. EC₅₀ values were averaged as their negative logarithms (pEC₅₀) * For these two cases, the extrapolated E_max exceeded the observed maximum observed potentiation by over 25%, but parameter SEM was not substantially increased, indicating that range of concentrations was adequate to project E_max. Higher drug concentrations could not be used due to solubility constraints.