Table 1.
Activity of OP and OC against molecular targets of high relevance for mood, cognition and behavior in binding or functional assays.
| Inhibition (% control)
|
||||
|---|---|---|---|---|
| OP
|
OC
|
|||
| 3 μM | 30 μM | 3 μM | 30 μM | |
| Radioligand binding assays | ||||
| GABA (non-selective)a | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| GABAA (central, BZD)a | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| GABAA (TBPS site)a | 6 | n.i.d. | n.i.d. | 2 |
| Dopamine D1 receptor | n.i.d. | n.i.d. | n.i.d. | 8 |
| Dopamine D2S receptor | 11 | 11 | 10 | 1 |
| Dopamine D3 receptor | 1 | n.i.d. | n.i.d. | 1 |
| Dopamine D4 receptor (D4.4 variant) | n.i.d. | n.i.d. | n.i.d. | 3 |
| Dopamine D5 receptor | n.i.d. | 2 | 2 | n.i.d. |
| AMPA-type glutamate receptor | 4 | 17 | n.i.d. | n.i.d. |
| Kainate-type glutamate receptor | n.i.d. | 14 | 10 | 10 |
| NMDA-type glutamate receptor (PCP) | 14 | 23 | 21 | 12 |
| NMDA-type glutamate receptor | n.i.d. | 6 | 12 | 10 |
| Glycine-site on NMDAR (strychnine-insensitive) | n.i.d. | n.i.d. | 1 | 24 |
| Metabotropic glutamate receptor 2b,c | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Metabotropic glutamate receptor 5b,c | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Serotonin 5-HT1A receptor | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Serotonin 5-HT1B receptor | 10 | 4 | n.i.d. | n.i.d. |
| Serotonin 5-HT1D receptor | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Serotonin 5-HT2A receptor | 4 | 13 | 15 | n.i.d. |
| Serotonin 5-HT2B receptor | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Serotonin 5-HT2C receptor | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Serotonin 5-HT3 receptor | n.i.d. | n.i.d. | 1 | n.i.d. |
| Serotonin 5-HT4e receptor | n.i.d. | 13 | n.i.d. | n.i.d. |
| Serotonin 5-HT5A receptor | 6 | n.i.d. | n.i.d. | n.i.d. |
| Serotonin 5-HT6 receptor | 6 | 3 | 3 | 6 |
| Serotonin 5-HT7 receptor | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Norepinephrine transporter | n.i.d. | n.i.d. | 5 | 11 |
| Dopamine transporter | 8 | 7 | 3 | 7 |
| GABA transporter | 15 | 15 | n.i.d. | 17 |
| Choline transporter (CHT1) | 9 | 5 | 14 | 14 |
| Serotonin transporter | n.i.d. | n.i.d. | 4 | n.i.d. |
| L-type Ca2+ channel (DHP site) | n.i.d. | n.i.d. | n.i.d. | 3 |
| L-type Ca2+ channel (diltiazem site) | 14 | 41 | 10 | 9 |
| L-type Ca2+ channel (verapamil site) | n.i.d. | 5 | n.i.d. | n.i.d. |
| N-type (voltage dep.) Ca2+ channel | 7 | n.i.d. | n.i.d. | n.i.d. |
| SK Ca2+ channel (non-selective) | n.i.d. | 2 | n.i.d. | n.i.d. |
| ATP sensitive K+ channel (Kir6.2) | 20 | 9 | 16 | 14 |
| Voltage gated K+ channel (a-DTX) | n.i.d. | n.i.d. | n.i.d. | −8 |
| Nicotinic acetylcholine receptor (α4β3, BGTX insensitive) | 5 | n.i.d. | n.i.d. | 11 |
| Na+ channel (site 2) | 11 | 38 | n.i.d. | 9 |
| Functional assays | ||||
| Acetylcholinesterase | n.i.d. | 1 | n.i.d. | n.i.d. |
| Monoaminoxidase A | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Monoaminoxidase B | n.i.d. | n.i.d. | 3 | n.i.d. |
| Metabotropic glutamate rec. 2b,c,d | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
| Metabotropic glutamate rec. 5b,c,d | n.i.d. | n.i.d. | n.i.d. | n.i.d. |
n.i.d.: No inhibition detected.
a
Binding data complemented with electrophysiological data on human GABAA α1β2γ2, Fig. S4 of Appendix A.
b
Assay performed at F. Hoffmann-La Roche Ltd.; all other assays performed at CEREP, Poitiers, France Laboratories, Le bois l’Evêque, 86600 Celle l’Evescault, France.
c
Assay performed in dose-response up to 30 μM.
d
Functional assay run in agonist and antagonist mode.