(±)-McN 5652 is a highly potent inhibitor of serotonin (5-HT, 5-hydroxytryptamine) uptake with a Ki value of approximately 0.6 nM in rat brain synaptosomes in vitro and an ED50 value of approximately 2 mg/kg p.o. ex vivo [1].
5-HT is a monoaminergic neurotransmitter to modulate numerous sensory, behavioural processes and motor in the mammalian nervous system [2]. There are at least three main groups of 5-HT receptor: 5-HT1, 5-HT2, and 5-HT3. Each group is not only structurally but also operationally distinct. Each receptor group has its own distinct transduction system. 5-HT4 is the more recently identified receptor. It almost represents a fourth 5-HT receptor class [3].
Receptor binding experiments indicated that McN-5652 has a weak affinity for serotonin 5-HT2 receptor (apparent Ki approximately 200 nM) and a very low affinity for serotonin 5-HT1 receptor [1].
In vivo, McN-5652 was required in low doses to potentiate the serotonin syndrome in rats. For this serotonin syndrome, the ED50 value was 1.5 mg/kg 2 hr after p.o. dosing. To potentiate head twitches which were induced by L-5-hydroxytryptophan (L-5HTP) in mice, the ED50 value is just 0.4 mg/kg 2 hr after p.o. dosing. That means McN-5652 is of high potency as a serotonin uptake inhibitor [1].
References:
[1]. Shank RP, Vaught JL, Pelley KA, et al. McN-5652: a highly potent inhibitor of serotonin uptake. J Pharmacol Exp Ther, 1988, 247(3):1032-8.
[2]. Tecott LH, Sun LM, Akana SF, et al. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature, 1995, 374(6522):542-6.
[3]. Hoyer D, Clarke DE, Fozard JR, et al. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev, 1994, 46(2):157-203.