Ki: 2, 6.9, and 1.7 μM for α1A, α1B, α1D, respectively

Midodrine is the prodrug of the α1-adrenergic receptor agonist, 1-(2’,5’-dimethoxyphenyl)-2-aminoethanol.

The α1-adrenergic receptor has some general functions similar with the α2-adrenergic receptor, but also has its own specific effects. α1-receptors primarily can mediate smooth muscle contraction and have other important functions as well.

In vitro: Midodrine was identified as a prodrug forming an active metabolite, desglymidodrine, which is an α1-receptor agonist exerting its actions through activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, leading to an increased vascular tone and elevation of blood pressure [1].

In vivo: A previous study was conducted to investigate the effect of intracerebroventricular injections of midodrine on the central nervous system of the rat. It was found that midodrine could decrease body temperature and increase locomotor activity, sedation in reserpinized rats as well as the cataleptic effect of haloperidol. Midodrine could also enhance amphetamine-stimulated locomotor activity and reduce the amphetamine and apomorphine sterotypy [1].

Clinical trial: The results of a previous pilot study indicated that midodrine combination with tolvaptan could better control ascites without any hepatic or renal dysfunction. Such combination therapy controled ascites rapidly as compared to midodrine or tolvaptan alone [2].

References:
[1] Kleinrok Z, Jagieo-Wójtowicz E, Oktaba-Polkowska A.  Central action of intraventricularly-injected midodrine in rats. Arch Int Pharmacodyn Ther. 1980 Oct;247(2):217-33.
[2] Rai N, Singh B, Singh A, Vijayvergiya R, Sharma N, Bhalla A, Singh V. Midodrine and tolvaptan in patients with cirrhosis and refractory or recurrent ascites: a randomised pilot study. Liver Int. 2017 Mar;37(3):406-414.