TABLE 1.
In vitro binding/activity profile of R-(+)- and S-(−)-cotinine
Values are expressed as the percent inhibition of specific binding or activity and represent the average of replicate tubes at each of the concentrations tested.
| Target | % Inhibition at 10 μM |
|
|---|---|---|
| R-(+)-Cotinine | S-(−)-Cotinine | |
| Neurotransmitter related | ||
| Adenosine transporter (h) | −4.49 | 2.82 |
| Adenosine, A1 | −0.85 | 4.94 |
| Adenosine, A2A (h) | −0.04 | 2.53 |
| Adrenergic, α1A | 2.59 | −0.33 |
| Adrenergic, α1B | 14.72 | 5.99 |
| Adrenergic, α2A (h) | 22.43 | −7.00 |
| Adrenergic, α2B | 2.65 | −2.32 |
| Adrenergic, α2C (h) | −7.89 | −3.08 |
| Adrenergic, β1 (h) | 2.20 | −0.31 |
| Adrenergic, β2 (h) | −5.54 | −16.48 |
| Dopamine transporter | 7.69 | −17.26 |
| Dopamine, D1 (h) | −7.16 | −3.22 |
| Dopamine, D2s (h) | 36.01 | 46.99 |
| Dopamine, D3 | 7.78 | 23.27 |
| Dopamine, D4.4 (h) | 30.28 | 17.99 |
| GABAA, agonist site | −7.61 | −6.46 |
| GABAA, BDZ, α 1 site | 0.01 | 3.96 |
| GABAB | 19.30 | 20.92 |
| Glutamate, AMPA site (ionotropic) | −6.15 | 1.03 |
| Glutamate, kainate site (ionotropic) | −2.93 | −2.82 |
| Glutamate, MK-801 site (ionotropic) | 0.17 | 1.94 |
| Glutamate, NMDA agonist site (ionotropic) | −6.41 | 2.42 |
| Glutamate, NMDA phencyclidine site (ionotropic) | 2.48 | −5.90 |
| Glutamate, NMDA glycine (stry-insens site) (ionotropic) | 14.39 | 12.77 |
| Glycine, strychnine-sensitive | −2.19 | −17.48 |
| Histamine, H1 | −7.03 | −1.34 |
| Histamine, H2 | −9.70 | 13.70 |
| Histamine, H3 | 6.58 | 4.23 |
| Muscarinic, M1 (h) | 8.81 | 6.20 |
| Muscarinic, M2 (h) | 13.10 | 0.47 |
| Muscarinic, M3 (h) | 3.90 | −1.39 |
| Muscarinic, M4 (h) | −17.19 | −10.25 |
| Muscarinic, M5 (h) | 13.28 | 9.04 |
| Nicotinic, neuronal (a-BnTx insensitive) | −4.99 | 1.33 |
| Norepinephrine transporter | −12.99 | 0.98 |
| Opioid, δ2 (h) | −13.02 | −7.11 |
| Opioid, μ (h) | 4.82 | −3.74 |
| Serotonin transporter | 9.62 | 10.68 |
| Serotonin, 5HT1A (h) | 9.51 | 17.11 |
| Serotonin, 5HT1D | 28.35 | 14.73 |
| Serotonin, 5HT2A | 2.26 | 8.25 |
| Serotonin, 5HT2C | 6.61 | 3.89 |
| Serotonin, 5HT3 | 11.44 | 4.39 |
| Serotonin, 5HT4 | 7.47 | −1.65 |
| Serotonin, 5HT5A (h) | 8.82 | −13.11 |
| Serotonin, 5HT6 (h) | 8.39 | −4.09 |
| Serotonin, 5HT7 (h) | 29.64 | 17.10 |
| Sigma 1 | −8.50 | −8.91 |
| Sigma 2 | −12.49 | −2.54 |
| Ion channels | ||
| Calcium channel, type L (dihydropyridine site) | −10.72 | −11.01 |
| Calcium channel, type N | 4.35 | 5.77 |
| GABA, chloride, TBOB site | 5.62 | −11.07 |
| Potassium channel, ATP-sensitive | 4.37 | 3.42 |
| Potassium channel, Ca2+ Act., VI | 2.04 | 9.16 |
| Potassium channel, I [Kr] (hERG) (h) | 0.91 | −8.57 |
| Sodium, site 2 | 26.72 | 23.98 |
| Second messengers | ||
| Nitric oxide, NOS (neuronal-binding) | −7.02 | 3.35 |
| Prostaglandins | ||
| Leukotriene, LTB4 (BLT) | 6.08 | 6.06 |
| Leukotriene, LTD4 (CysLT1) | 1.87 | 5.42 |
| Thromboxane A2 (h) | −16.05 | −4.82 |
| Brain/gut peptides | ||
| Angiotensin II, AT1 (h) | 8.14 | 6.73 |
| Bradykinin, BK2 | −0.84 | −1.20 |
| Endothelin, ET-A (h) | −3.19 | 5.19 |
| Neurokinin, NK1 | 6.48 | 17.49 |
| Neuropeptide, NPY2 (h) | −14.58 | −2.44 |
| Enzymes | ||
| Esterase, acetylcholine | −5.12 | −1.22 |
| Phosphodiesterase, PDE3A1A (h) | 8.72 | 3.36 |
| Phosphodiesterase, PDE5A1 (h) | 5.21 | 3.41 |
| Enzymes, kinases | ||
| Kinase, protein, PKA (h) | 13.42 | 13.63 |
| Kinase, protein, PKCa (h) | −12.42 | −6.87 |
AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BDZ, benzodiazepine; BLT, high affinity receptor for the leukotriene LTB4; hERG, human ether-à-go-go–related gene; 5HT, 5-hydroxytryptamine; NMDA, N-methyl-d-aspartate; PKA, protein kinase A; PKCa, protein kinase C α; TBOB, t-butyl bicyclo-orthobenzoate.