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Midodrine is a prodrug which forms the active metabolite, desglymidodrine, which is an α 1-adrenergic receptor agonist and exerts its actions via activation of α 1-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure.
Desglymidodrine (developmental code name ST-1059) is the active metabolite of the prodrug antihypotensive agent midodrine. [1] [2] [3] It acts as a selective α 1-adrenergic receptor agonist. [1] [2] [3] Desglymidodrine is formed from midodrine via deglycination. [1] [2] [3]
Droxidopa is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitter norepinephrine (noradrenaline). [4] Hence, it acts as a non-selective agonist of the α-and β-adrenergic receptors. Unlike norepinephrine, but similarly to levodopa (L-DOPA), droxidopa is capable of crossing the protective blood–brain barrier (BBB). [4]
A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. [1] [2] Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug is absorbed, distributed, metabolized, and excreted . [3] [4]
Levodopa (L-DOPA), a prodrug of dopamine which is used to treat Parkinson's disease and certain other conditions. A neurotransmitter prodrug, or neurotransmitter precursor, is a drug that acts as a prodrug of a neurotransmitter. A variety of neurotransmitter prodrugs have been developed and used in medicine.
[2] [3] [4] It is said to be similarly or less effective than midodrine in the treatment of orthostatic hypotension and shows substantially lower potency. [5] [1] The drug is a selective α 1-adrenergic receptor agonist [6] but is also said to have β-adrenergic receptor agonist activity. [1]
The gene is located on chromosome 22q13.1. near two cytochrome P450 pseudogenes (CYP2D7P and CYP2D8P). [16] Among them, CYP2D7P originated from CYP2D6 in a stem lineage of great apes and humans, [17] the CYP2D8P originated from CYP2D6 in a stem lineage of Catarrhine and New World monkeys' stem lineage. [18]
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