XC-101
Pharmaceutical compound
From Wikipedia, the free encyclopedia
XC-101, or XC101, also known as XC101-D13H, is a non-selective serotonin receptor modulator which is under development for the prevention of migraine.[1][3][4][2][5] It is taken orally.[1][2][3]
| Clinical data | |
|---|---|
| Other names | XC101; XC101-D13H; XC-101-D13H |
| Routes of administration | Oral[1][2][3] |
| Drug class | Serotonin 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT7 receptor agonist; Serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor antagonist; Antimigraine agent |
| Pharmacokinetic data | |
| Onset of action | 2–3 hours (Tmax)[2] |
| Elimination half-life | 10–15 hours[2] |
The drug acts as an agonist of the serotonin 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT7 receptors and as an antagonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, with varying potencies at these targets.[1][2] Its antimigraine preventative efficacy is thought to derive specifically from its serotonin 5-HT2B and 5-HT2C receptor antagonism, although its serotonin 5-HT1D and 5-HT1B receptor agonism may also contribute.[2][6][7][8] Due to its lack of agonism at the serotonin 5-HT2A and 5-HT2B receptors and at the α1A-adrenergic receptor, XC-101 is thought to avoid adverse effects and toxicity including hallucinogenic effects, cardiac fibrosis and valvulopathy, and vasoconstriction.[2] The pharmacokinetics and tolerability of XC-101 at doses of 0.2 to 0.5 mg orally in humans have been studied.[6][7][2]
Besides XC-101, its developer has also studied ergoline antimigraine agents like methysergide.[9][10][4][5][3] XC-101 has been compared to methysergide, which was described as being effective for migraine prevention but as having serious side effects due to undesirable off-target activities.[4][5] Whereas methysergide is functionally an agonist of the serotonin 5-HT2B receptor due to its active metabolite methylergometrine, XC-101 is a silent antagonist of the receptor.[9][2] In addition, whereas methysergide was found to be a full agonist of the serotonin 5-HT2A receptor, which is associated with psychedelic effects, XC-101 was likewise a silent antagonist of the receptor.[9][2]
XC-101 was first described in the scientific literature by 2019.[4][5][2] It is under development by Xoc Pharmaceuticals.[1] As of November 2022, the drug is in phase 1/2 clinical trials for migraine prevention.[1] The chemical structure of XC-101 does not yet appear to have been disclosed.[1] However, Xoc Pharmaceuticals patented an ergoline antimigraine compound with code name "D13H" in 2019 and this compound may be XC101-D13H (XC-101).[11] It is the 2-cyclopropyl and 9,10-dihydro analogue of methysergide (or 2-cyclopropyl-9,10-dihydromethysergide).[11]