Migraine

Rimegepant (BMS-927711; BHV-3000) is an orally bioavailable and blood-brain barrier permeable antagonist of CGRP and AMY1 receptors, with a pIC₅₀ of 8.01 and a K_i of 0.027 nM for human CGRP receptors. Rimegepant antagonizes cAMP production induced by αCGRP, βCGRP and amylin at CGRP and AMY1 receptors in humans, rats and mice, as well as at rat AMY3 receptors. Rimegepant can be used in research related to migraine .

Dihydroergotamine (DFN-19) is a blood-brain barrier-permeable semi-synthetic ergot alkaloid, acting as a full agonist of 5-HT1B/1D receptors (K_i values of 0.3 nM and 2.5 nM, respectively; functional IC₅₀ values of 2 nM and 2.2 nM, respectively). Dihydroergotamine inhibits Forskolin (HY-15371)-stimulated cAMP accumulation, possesses α-adrenergic receptor antagonistic activity and weak dopaminergic agonistic activity. It mediates intracranial cerebrovascular contraction, inhibits the release of neuropeptides such as CGRP/substance P, and suppresses neurogenic inflammation by activating 5-HT1B/1D receptors in the trigeminovascular system. Dihydroergotamine binds to the catalytic site of Trypanosoma cruzi trypanothione reductase and exhibits trypanocidal activity in vitro. Dihydroergotamine can be used in studies related to migraine and trypanosome infections.

Dihydroergotamine mesylate is a blood-brain barrier-permeable semi-synthetic ergot alkaloid, acting as a full agonist of 5-HT1B/1D receptors (K_i values of 0.3 nM and 2.5 nM, respectively; functional IC₅₀ values of 2 nM and 2.2 nM, respectively). Dihydroergotamine mesylate inhibits Forskolin (HY-15371)-stimulated cAMP accumulation, possesses α-adrenergic receptor antagonistic activity and weak dopaminergic agonistic activity. It mediates intracranial cerebrovascular contraction, inhibits the release of neuropeptides such as CGRP/substance P, and suppresses neurogenic inflammation by activating 5-HT1B/1D receptors in the trigeminovascular system. Dihydroergotamine mesylate binds to the catalytic site of Trypanosoma cruzi trypanothione reductase and exhibits trypanocidal activity in vitro. Dihydroergotamine mesylate can be used in studies related to migraine and trypanosome infections.

Galcanezumab (LY 2951742) is a humanized IgG4 monoclonal antibody against the CGRP ligand. Galcanezumab can be used for migraine or cluster headaches research.

Erenumab (AMG-334) is a fully human monoclonal antibody. Erenumab inhibits the calcitonin gene-related peptide (CGRP) receptor. Erenumab prevents the increase in dermal blood flow in cynomolgus monkeys. Erenumab can be used in the research of episodic migraine.

Senkyunolide I is an orally active, blood-brain barrier-permeable metabolite of Z-ligustilide (HY-N0401A). Senkyunolide I is isolated from Ligusticum chuanxiong. Senkyunolide I upregulates p-Erk1/2 and Nrf2/HO-1, and inhibits Caspase 3. Senkyunolide I alleviates Apoptosis. Senkyunolide I increases the pain threshold in mice and reduces acetic acid-induced writhing responses in mice. Senkyunolide I improves neurological deficits, reduces infarct volume and alleviates cerebral edema in rats with focal cerebral ischemia-reperfusion injury. Senkyunolide I protects renal function and structural integrity in a mouse model of renal ischemia-reperfusion injury. Senkyunolide I is applicable to research related to focal cerebral ischemia-reperfusion injury, migraine, and renal ischemia-reperfusion injury.

Fonagepant (FE 205030) is a calcitonin gene-related peptide (CGRP) receptor antagonist with an IC₅₀ of 0.2 nM. Fonagepant selectively blocks CGRP receptor activity, inhibits CGRP-induced vasodilation, attenuates capsaicin-induced increase in skin blood flow, and blocks CGRP-induced vasodilation in isolated human mesenteric resistance arteries. Fonagepant can be used in studies related to acute migraine attacks.

Dihydroergotamine-d₃ is the d₃-labeled Dihydroergotamine (HY-B0670). Dihydroergotamine (DFN-19) is a blood-brain barrier-permeable semi-synthetic ergot alkaloid, acting as a full agonist of 5-HT1B/1D receptors (K_i values of 0.3 nM and 2.5 nM, respectively; functional IC₅₀ values of 2 nM and 2.2 nM, respectively). Dihydroergotamine inhibits Forskolin (HY-15371)-stimulated cAMP accumulation, possesses α-adrenergic receptor antagonistic activity and weak dopaminergic agonistic activity. It mediates intracranial cerebrovascular contraction, inhibits the release of neuropeptides such as CGRP/substance P, and suppresses neurogenic inflammation by activating 5-HT1B/1D receptors in the trigeminovascular system. Dihydroergotamine binds to the catalytic site of Trypanosoma cruzi trypanothione reductase and exhibits trypanocidal activity in vitro. Dihydroergotamine can be used in studies related to migraine and trypanosome infections.

Eptinezumab (ALD-403) is a human monoclonal antibody targeting the α and β subtypes of human calcitonin gene-related peptide (CGRP). Eptinezumab binds to the CGRP ligand and blocks its binding to endogenous CGRP receptors, thereby inhibiting receptor activation. Eptinezumab can be used in research related to migraine.

Rimegepant (BMS-927711) sulfate hydrate is a potent, orally active, selective and competitive calcitonin gene-related peptide (CGRP) receptor antagonist with a K_i of 0.027 nM and an IC₅₀ of 0.14 nM for hCGRP receptor. Rimegepant sulfate hydrate can be used for migraine research.

Vinyl-L-NIO (L-VNIO) hydrochloride is a neuronal nitric oxide synthase (NOS) inhibitor with a rat K_i of 0.10 μM. Vinyl-L-NIO hydrochloride inhibits NADPH oxidase activity, attenuates renal fibrosis, inflammation, oxidative stress indices, and albuminuria. Vinyl-L-NIO hydrochloride can be used for the research of parkinson's disease, migraine headache, and hypertension.

PL37 (Debio-0827) is an orally active, blood-brain barrier permeable dual enkephalinase inhibitor. PL37 inhibits aminopeptidase N, neprilysin, and metalloproteases, thereby blocking the degradation of endogenous enkephalins, elevating enkephalin levels, and activating peripheral μ- and δ-opioid receptors. PL37 induces mitochondrial dysfunction, mitophagy, and apoptosis, inhibits endothelial cell proliferation, migration, invasion, and tube formation, and suppresses hemangioma tumor growth and angiogenesis. PL37 can be used in research related to peripheral neuropathic pain, osteosarcoma-induced hyperalgesia, painful diabetic neuropathy, migraine, bone cancer pain, neuroinflammatory pain, and infantile hemangioma.

(Rac)-LY-2300559 is a positive allosteric modulator of metabotropic glutamate receptor 2 (mGlu2) and an antagonist of cysteinyl leukotriene 1 (CysLT1) receptor, with both EC₅₀ and IC₅₀ values less than 12.5 μM. (Rac)-LY-2300559 enhances glutamate-induced mGlu2 receptor signaling while exerting antagonistic activity against the CysLT1 receptor. (Rac)-LY-2300559 can be used in migraine-related research.

Mabuprofen (Aminoprofen) is an amide derivative of Ibuprofen (HY-78131) and a COX inhibitor. Mabuprofen inhibits prostaglandin biosynthesis, thereby reducing inflammation, relieving pain and lowering body temperature. Mabuprofen is applicable to research related to arthritis, muscle pain, inflammatory diseases, headache and toothache.

Phenopyrazone (Diphenox), a derivative of Antipyrine (HY-B0171), exhibits oral activity as well as analgesic, antipyretic, anti-inflammatory, and antidiarrheal properties. Phenopyrazone can be used in research related to headache, rheumatism, chronic diarrhea and varicose veins.

5-HT2A receptor agonist-14 (Compound I-23) is a tricyclic 5-HT2A receptor agonist with a pEC₅₀ value ≥ 6. 5-HT2A receptor agonist-14 can be used in research related to depression, anxiety, substance abuse and headache.

BTS 72664 is a broad-spectrum, non-sedating, orally effective anticonvulsant. Its anticonvulsant effect mainly arises from enhancing GABA_A receptor (GABA_A receptor)-mediated chloride channel currents, while it exerts weak blocking effects on Na⁺ channels (K_i = 350 μM) and NMDA receptors (NMDA receptor) (IC₅₀ = 43 μM). BTS 72664 prevents the elevation of extracellular glutamate, glycine and serine concentrations in neurons, reduces cerebral infarct size, promotes functional recovery, prevents multiple types of epileptic seizures, and has low sedative potential. BTS 72664 can be used for the research of epilepsy, stroke and migraine.

Lerimazoline is a selective 5-HT1D receptor agonist with K_i values of 72 and 3480 nM for h5-HT1D and h5-HT1B. Lerimazoline inhibits Forskolin (HY-15371)-stimulated cAMP production and induces contractions in rabbit saphenous vein preparations. Lerimazoline can be used for the research of migraine.

Nicotinanilide (N-Phenylnicotinamide) (Compound 12) is an aquaporin 4 (AQP4) inhibitor. Nicotinanilide can be used for research on diseases associated with AQP4 dysfunction, such as epilepsy and migraine.

O-1812 is a selective CB₁ ligand. O-1812 is also a very weak AMT inhibitor. O-1812 can be used in the research of chronic pain, migraines, and inflammation.