Introduction

The 5-HT₁ receptors are a subfamily of the 5-HT serotonin receptors that bind to the endogenous neurotransmitter serotonin (also known as 5-hydroxytryptamine, or 5-HT). The 5-HT₁ subfamily consists of five G protein-coupled receptors (GPCRs) that share 40% to 63% overall sequence homology, including 5-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_1E, and 5-HT_1F. Receptors of the 5-HT₁ type, specifically, the 5-HT_1A and 5-HT_1D receptor subtypes, are present on the cell bodies. Receptors of the 5-H_T1 type, specifically, the 5-HT_1B and 5-HT_1D receptor subtypes, are also present on the nerve terminals. These receptors are broadly distributed throughout the brain and are recognised to play a significant part in regulating synaptic levels of 5-HT.

The receptor subfamily is coupled to G_i/G_o and mediate inhibitory neurotransmission by inhibiting the function of adenylate cyclase and modulating downstream ionic effects. This R-coupling to G_i/G_o proteins leads to a reduction in local concentrations of cAMP, proving that 5-HT₁ are primarily inhibitory. There is no 5-HT_1C receptor, as it was reclassified as the 5-HT_2C receptor.

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