Dapoxetine hydrochloride

K_V4 channels, also known as Shal-type K⁺ channels, are expressed in a variety of tissues, with particularly high levels in the brain and heart. These channels contribute to transient, voltage-dependent K⁺ currents in the nervous system and heart¹. K_V1 channels are also expressed in various tissues and are usually activated by membrane depolarization².

Dapoxetine hydrochloride, also known as “Priligy,” is a synthetic, high affinity K_V4.3 and K_V1.5 blocker and is also a competitive 5-HT re-uptake inhibitor. Dapoxetine hydrochloride has an effective concentration of 5-300 μM with an IC₅₀ of 5.3 and 11.6 μM on cloned K_V4.3 and K_V1.5 channels, respectively. Dapoxetine reduces the peak amplitude of K_V4.3 currents and also accelerates the decay rate of current inactivation in a concentration-dependent manner. The block of the K_V4.3 channel by dapoxetine is highly voltage-dependent at a membrane potential coinciding with the activation of the channel. Dapoxetine blocks K_V4.3 currents by binding to the open state of the channels and by accelerating the closed-state inactivation. Until recently, it was believed that most of Dapoxetine’s (and other SSRI’s) pharmacological activities are attributed to 5-HT reuptake inhibition. This effect is used for the management of General anxiety disorder (GAD), obesity, neuropathic pain, premature ejaculation and other medical conditions. It has, however, been hypothesized that Dapoxetine’s therapeutic effects are also achieved through interaction with other types of channels as well as K_V type channels³.