Are 5-HT₁ receptor agonists effective anti-migraine drugs?

Figures & data

Figure 1. Structures of ergotamine, sumatriptan, and lasmiditan

Table 1. Clinically approved antimigraine drugs and their targets. 5-HT1A-D: 5-hydroxytryptamine receptors subtypes, A-D: adrenergic receptors subtypes, D1-2: dopamine receptor subtypes [3–5]

Drugs	Pharmacologically active targets	Pharmacologically inactive targets	Pharmacologically unknown action
Ergotamine	5-HT1B/D, 5-HT2A α1A, α1B, α1D	-	5-HT1A/F,5-HT2B/C α1 C D1/2
Sumatriptan	5-HT1A/B/D/F	-	-
Naratriptan	5-HT1A/B/D/F	-	-
Zolmitriptan	5-HT1B/D/F	5-HT1A, 5-HT2A/B, 5-HT7	5-HT1E
Rizatriptan	5-HT1B/D/F	-	-
Almotriptan	-	-	5-HT1B/D
Frovatriptan	5-HT1B/D/F	5-HT1A, 5-HT2A/B, 5-HT7	5-HT1E
Eletriptan	5-HT1B/D/F	-	5-HT1A, 5-HT1E 5-HT2B, 5-HT7
Lasmiditan	5-HT1F	-	-

Table 2. 5-HT1 receptor subtypes, location of expression pertaining to migraine, functions and ligands clinically approved for migraine [3–5]

5-HT1 receptor subtypes	Location pertaining to migraine	Main functions	Agonists
5-HT1A	Central nervous system Blood vessel	Addiction Aggression Aggression Anxiety Learning Memory Mood Nausea Nociception Sleep Sociability Vasoconstriction	Sumatriptan Naratriptan
5-HT1B	Central nervous system Blood vessel	Addiction, Aggression Anxiety Learning Memory Mood Vasoconstriction	Ergotamine Sumatriptan Naratriptan Zolmitriptan Rizatriptan Eletriptan
5-HT1D	Central nervous system Blood vessel	Anxiety Vasoconstriction	Ergotamine Sumatriptan Naratriptan Zolmitriptan Rizatriptan Eletriptan
5-HT1F	Central nervous system	Migraine	Sumatriptan Naratriptan Zolmitriptan Rizatriptan Eletriptan Lasmiditan

Figure 2. L-tryptophan metabolism: the methoxyindole and kynurenine pathways. A majority of tryptophan (TRP) is metabolized through the TRP-kynurenine (KYN) pathway, catalyzed by several key enzymes including indoleamine 2,3-dioxygenase (IDO) 1, IDO 2, tryptophan-2,3-dioxygenase (TDO), and kynurenine 3-monooxygenase (KMO) into several bioactive metabolites including kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykinurenine, anthranilic acid (ANA), xanthurenic acid (XA), 3-hydroxyanthuranilic acid, 5-hydroxyindoleacetic acid, xanthurenic acid (XA), and quinolinic acid. IDO 1, IDO 2, and KMO enzymes and KYN metabolites were shown to be involved in the pathogenesis of migraine