2-(4-chlorophenyl)guanidine and phenylguanidine

Human organic cation transporters (OCTs) represent an understudied neurotransmitter uptake mechanism for which no selective agents have yet been identified. Several neurotransmitters (e.g. serotonin, norepinephrine) are low-affinity substrates for these transporters, but possess higher affinity for other transporters (e.g. the serotonin or norepinephrine transporters; SERT and NET, respectively). We have identified a new class of OCT inhibitors with a phenylguanidine structural scaffold. Here, we examine the actions of a series of such compounds and report preliminary structure-activity relationships (SARs) - the first dedicated SAR study of OCT3 action. Initial results showed that the presence of a substituent on the phenyl ring, as well as its position, contributes to the phenylguanidines' inhibitory potency (IC

Topics: Dose-Response Relationship, Drug; Guanidines; Humans; Molecular Structure; Organic Cation Transport Proteins; Structure-Activity Relationship

Topics: Binding Sites; Guanidines; Humans; Molecular Structure; Structure-Activity Relationship; Trypsin Inhibitors; Urokinase-Type Plasminogen Activator