Ergotamine and nicergoline – Facts and myths

Abstract

Ergotamine, being a representative of naturally occurring ergoline alkaloids, derived from d-lysergic acid, and nicergoline, a d-lumilysergic acid derivative belonging to semi-synthetic ergot-derived alkaloids, display diversified affinity for adrenergic, serotoninergic, and dopamine receptors. Although introduction of triptans marginalized use of ergotamine, nicergoline is used in cerebral metabolic-vascular disorders, and dementia. Additionally, nicergoline exhibits a safety profile comparable to that of placebo, and none of the reviewed studies reported any incidence of fibrosis or ergotism with nicergoline treatment. In line with the recent data, activation of 5-HT2B receptor by ergot derivatives i.e. ergotamine, methysergide, pergolide, and carbegoline is involved in pathogenesis of drug-induced valvulopathy. In contrary structurally related drugs - lisuride and terguride do not increase the risk of valvular heart disease. It seems, that more detailed mechanistic studies on nicergoline and ergotamine might be beneficial for determining structural requirements related to activation of G-protein as well as alternative signal transduction pathways e.g. β-arrestins or different kinases, and responsible for drug liabilities.

Role of Nicergoline in Corneal Wound Healing in Diabetic Rats

“…To date, this is the rst experimental, controlled, and double-blind study to investigate the potential of nicergoline to improve the rate of corneal reepithelization and to treat corneal ulcers in a clinical context of diabetes, since the other studies in the literature evaluated this drug only in healthy animals. 13,14,19 The current study exhibits some limitations. It is important to mention the lack of proof of diabetic neuropathy by an objective test, such as the corneal sensitivity test with the Cochet-Bonnet esthesiometer.…”

“…Such properties have inspired research into its use in corneal wound healing. 13,14,15,16,17,18 In a previous study, nicergoline contributed to the corneal reepithelialization of 110 eyes from 100 rats, and corneal NGF protein was higher in the nicergoline-treated group than in the control group. 16 In another experimental study that assessed 10 eyes from 5 healthy dogs without a control group, the effect of nicergoline on the ocular surface was assessed using corneal esthesiometry, Schirmer's test 1, and tear lm break-up time, but the drug did not signi cantly alter canine ocular surface parameters.…”

Allodynia Is Associated With Initial and Sustained Response to Acute Migraine Treatment: Results from the American Migraine Prevalence and Prevention Study

“…17 Regarding the other drugs, opioids are usually excitatory, rather than inhibitory in the dorsal horn, 37,38 potentially by interfering with glutamate clearance from the synapse 39 ; barbiturates, which suppress neuronal firing by increasing chloride conductance through its binding to the GABA A receptor, 40 are thought to achieve their therapeutic effects mainly by increasing GABA level in supraspinal brain areas rather than in the spinal cord 41 ; and ergot alkaloids are thought to exert their anti-migraine effects by acting mainly on peripheral tissues (through 5-HT 1,2 receptors, a1and a2-adrenoceptors, and D 2 -like dopamine receptors) to prevent release of vasoactive neuropeptides and cause vasoconstriction of peripheral blood vessels. [42][43][44][45][46][47][48] The peripheral activity of ergot alkaloids, as well as their being the only migraine-specific medications besides triptans that were assessed, may help to explain why individuals using them did not differ from triptan users on the 2hPF outcome. This result may also be due to a potentially faster onset of intranasal and injectable forms of ergot alkaloids.…”

Alteration in plasma and striatal levels of d -serine after d -serine administration with or without nicergoline: An in vivo microdialysis study

“…From the pharmacological perspective, Nic can elicit a high affinity for α 1 -adrenergic and 5-HT 1A receptors and act as an antagonist at these sites. By blocking the α 1 -adrenergic receptors, Nic is able to improve brain hemodynamics and metabolism, increasing energy production [32] . In fact, Nic has positive effects on several aspects of human cognitive performance, psychomotor performance, attention, reaction times, and other indicators of brain function [33] .…”