5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.
The serotonin receptors modulate the release of many neurotransmitters, such as glutamate, GABA, dopamine, epinephrine / norepinephrine, acetylcholine. And it slao modulate the release of many hormones, including oxytocin, prolactin, vasopressin, cortisol, corticotropin, and substance P, among others. Serotonin receptors influence various biological and neurological processes such as aggression, appetite, cognition, learning, sleep, and thermoregulation and so on. They are the target of a variety of pharmaceutical and recreational drugs. For exmple, many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.
The alpha-2 (α2) adrenergic receptor (or adrenoceptor) is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α2-adrenergic receptor in the central and peripheral nervous systems.
Spiroxatrine is a selective, dual antagonist of 5-HT1α and α2-adrenergic for Nerve Injury Research
Spiroxatrine (R 5188) is a selective, dual antagonist of 5-HT1α and α2-adrenergic, with the Ki values of 3.94, 224000, 118.5 nM for 5-HT1α, 5-HT1β and 5-HT2, respectively. And it has a sedative effect.
In Vitro, Spiroxatrine (0.01-0.1 μM, 15 mins) increases contraction in vas deferenstissues from α2A/D-adrenoceptor knockout mice. In Vivo, Spiroxatrine (1-25 ug for i.p., 5 days) increases hindpaw withdrawal latencies to thermal and mechanical stimulation in the nerve injury rat and Carrageenan-induced rat inflammation model. What’s more, Spiroxatrine (4 mg/kg/day for i.p., 5 mins) increases the voluntary oral ethanol intake induced by Fluoxetine in the selectively bred alcohol-preferring P line of rats.
In conclusion, Spiroxatrine is a 5-HT1α/α2-adrenergic antagonist for nerve injury research.