Telcagepant (MK-0974) is a calcitonin gene-related peptide receptor antagonist. Merck & Co was developing telcagepant for the treatment of pain. Telcagepant is an extremely potent CGRP antagonist with a Ki = 0.77 (0.07 nM). Telcagepant showed efficacy against acute migraines; however, different patient populations may show more beneficial effects with telcagepant versus triptans. In the acute treatment of migraine, Telcagepant was found to have equal potency to rizatriptan and zolmitriptan in two Phase III clinical trials. Merck & Co has now terminated development of the drug.

Carabersat is an anticonvulsant devoid of cardiovascular side effects with minimal central nervous system adverse actions. Carabersat does not bind to ion channels, purinergic, aminergic, opioid and other peptidergic receptors. It selectively interacts with its own binding site, which is not yet elucidated. Carabersat has no effect on sodium channels, GABAergic or glutamate pathways. Carabersat had been in phase II clinical trials for the treatment of epilepsy. It has a potential action in preventing migraines because it acts through an inhibition of the cortical spreading depression trigeminal nerve-induced vasodilatation in cats. Its good therapeutic index and the markedly reduced neurological impairments could make it a useful agent for migraine prophylaxis pending efficacy parameters of controlled studies, which are underway.

Betonicine (trans-2-carboxy-4-hydroxy-1,1,-dimethylpyrrolidinium hydroxide, inner salt) and its cis isomer, turicine, are naturally occurring substituted pyrrolidines. Betonicine was used as an analgesic 1000 years ago and is still available commercially from herbalists today. Betonicine has been isolated from Achillea millefolium L. (Compositae) and probably from A. atrata L. (Compositae); it is an alkaloid. Proline betaine and Betonicine were identified as metabolically inert cell protectants against extremes in osmolarity and growth temperatures.

S-fluoxetine is an enantiomer of fluoxetine, a potent and selective inhibitor of the neuronal serotonin-uptake carrier and a clinically effective antidepressant. R-fluoxetine and S-fluoxetine enantiomers are nearly equipotent at blocking serotonin reuptake. In all biochemical and pharmacological studies, the eudismic ratio for the fluoxetine enantiomers is also near unity. A study examining the relative contributions of CYP enzymes to the metabolism of S-fluoxetine, and R-fluoxetine found dramatic differences. These data led to discovery programs between Lilly and Sepracor for the individual enantiomers. S-fluoxetine was studied in a phase 2 clinical trial for the prophylaxis of migraine, however, development was discontinued.

alpha-N-methyl-histamine is a metabolite of histamine that plays an important role in several (patho) physiological processes. alpha-N-methyl-histamine is being a potent agonist of histamine H3 receptor can be used as an effective therapeutic alternative in migraine patients.

Isometheptene (usually as isometheptene mucate) is a sympathomimetic amine sometimes used in the treatment of migraines and tension headaches due to its vasoconstricting properties. Isometheptene's vasoconstricting properties arise through activation of the sympathetic nervous system via epinephrine and norepinephrine. These compounds elicit smooth muscle activation leading to vasoconstriction by interacting with cell surface adrenergic receptors.

Isometheptene (usually as isometheptene mucate) is a sympathomimetic amine sometimes used in the treatment of migraines and tension headaches due to its vasoconstricting properties. Isometheptene's vasoconstricting properties arise through activation of the sympathetic nervous system via epinephrine and norepinephrine. These compounds elicit smooth muscle activation leading to vasoconstriction by interacting with cell surface adrenergic receptors.

Isometheptene (usually as isometheptene mucate) is a sympathomimetic amine sometimes used in the treatment of migraines and tension headaches due to its vasoconstricting properties. Isometheptene's vasoconstricting properties arise through activation of the sympathetic nervous system via epinephrine and norepinephrine. These compounds elicit smooth muscle activation leading to vasoconstriction by interacting with cell surface adrenergic receptors.

Isometheptene (usually as isometheptene mucate) is a sympathomimetic amine sometimes used in the treatment of migraines and tension headaches due to its vasoconstricting properties. Isometheptene's vasoconstricting properties arise through activation of the sympathetic nervous system via epinephrine and norepinephrine. These compounds elicit smooth muscle activation leading to vasoconstriction by interacting with cell surface adrenergic receptors.

L-acetylcarnitine or acet-L-carnitine, a compound, naturally produced by the body, is necessary for fatty-acid metabolism and energy production. It is often taken as a dietary supplement. The mechanisms of action of acetylcarnitine have not been fully elucidated, but it seems that the main role of acetylcarnitine is to donate an acetyl group during fatty acid metabolism to help transport fatty acids, such as acetyl CoA, into the mitochondrial matrix where fatty acid metabolism occurs. L-acetylcarnitine is an investigational drug, which is approved in some countries, for example in Italy for diabetic neuropathy. Phase IV of clinical trials have revealed, that it also effective agent to treat the Alzheimer's disease. In contrary, the efficacy of L-acetylcarnitine as a prophylaxis in migraine patients did not provide evidence of benefit for efficacy. Besides, Acetyl-L-carnitine was in clinical trial Phase III to investigate its efficacy in the treatment of peripheral sensory neuropathy that anti-cancer chemotherapeutics induce. Recently published article unexpectedly discovered that this drug increased chemotherapy-induced peripheral neuropathy in a randomized trial.