TABLE 2

Functional activity of bicifadine at neurotransmitter receptors and transporters The functional activity of bicifadine was tested in physiological or biochemical systems where its binding affinity (Ki) was determined to be less than 10 μM (Table 1). Studies were performed at: 1Oregon Health Sciences University/VA Medical Center; 2MDS Pharma Services; 3Cerep; 4Rehovot University.


Receptor /Transporter System

Preparation

Stimulus

Actions
Norepinephrine transporter Recombinant human transporters1 [3H]NE uptake by intact cells Antagonist, inhibits uptake, IC50 = 55 ± 3.4 nM
Serotonin transporter Recombinant human transporters1 [3H]5-HT uptake by intact cells Antagonist, inhibits uptake, IC50 = 117 ± 26 nM
Dopamine transporter Recombinant human transporters1 [3H]DA uptake by intact cells Antagonist, inhibits uptake, IC50 = 910 ± 140 nM
α1-Adrenergic Rat vas deferens2 Phenylephrine (2 μM)-induced contractions Antagonist, inhibits phenylephrine induced contractions, IC50 = 18.6 μM
α2-Adrenergic Rat vas deferens2 Neurogenic twitch Agonist, reduces twitch response, EC50 = 6 μM
β1-Adrenergic Guinea pig left atrium2 Isoproterenol (50 nM)-induced positive inotropy Antagonist, blocks inotropy, IC50 = 22.4 μM
5-HT1A-Serotonergic Recombinant human receptors3 5-HT (30 nM)-stimulated [35S]GTPγS binding Agonist, enhances binding, EC50 = 10 μM
5-HT1B-Serotonergic Rat caudal artery rings2 Serotonin (1 μM)-stimulated contractions Antagonist, blocks contractions, IC50 = 22 μM
NMDA Receptor
Primary cultures of hippocampal pyramidal neurons4
Glycine-dependent, NMDA (5–1000 μM)-stimulated ion currents
IC50 = 217 ± 18 μM
  • GTPγS, guanosine 5′-3-O-(thio)triphosphate