Pharmacology Article Critique: Ergot Alkaloids
Introduction and Summary
The article Ergot Alkaloids: A Review on Therapeutic Applications covers the basics of ergot alkaloids through their source, basic structure, and therapeutic applications. The article expounds on the homology of the structure of ergot alkaloids to exploit the basis of the therapeutic applications. The therapeutic applications are drawn from the observations made on the disease called Ergot of Rye in plants. The disease stems from infection of grains in grass and cereals with the fungus Claviceps purpurea. It is from these plants that the alkaloids are harvested. The naturally obtained ergot alkaloids from these plan parts possess a tetracyclic ergoline ring, which is the same functional group found in neurotransmitters like serotonin, dopamine, and noradrenaline. The possession of this functional group confers the ability to target action sites that are targeted by neurotransmitters. As such, ergotamine alkaloids have been manipulated over time to be effective in the treatment of neural conditions. This paper provides a summary and critique of this article, assessing its suitability as an educational piece in ethno-pharmacology.
The article expounds on the formation of ergot in grass and cereals and the occurrence of the symptoms through the formation of ergot bodies in the place of the normal kernels instead of kernels. In cereals and grass, the only affected plant part is the ovary since the fungus does not spread. Ergotamine is the most prevalent alkaloid present in the sclerotium of the formed ergot. However, other peptide alkaloids are still present that are a part of the ergotamine class. The presence of the Claviceps purpurea infection in rye predisposes individuals to suffer from the symptoms of hallucinations, upset of the GIT, and pain and heat in the limbs. Due to the symptoms, the disease was given the name ‘Holy Fire.’ However, the symptoms of the disease caused by consumption of contaminated rye for bread were an eye-opener towards the development of therapeutic uses for the infection.
The toxicity of infected rye by the fungus was manipulated to include the metabolites in drugs. The use of ergot in medicine spans more than a century. The active component of Ergot-containing drugs is ergotamine and not lysergic acid diethylamide (LSD). However, ergotamine is metabolized to lysergic acid which serves as the precursor in the anabolism of LSD. The pharmacological actions of alkaloids are manifested through their action on dopamine receptors. Ergot alkaloids act as agonists to these receptors. On the other hand, ergot alkaloids also inhibit the action of prolactin. Apart from the action on the neurotransmitter and hormonal system, the alkaloids also act on blood vessels, leading to vasoconstriction and reduction in bleeding as a result. The action mechanisms have been manipulated in the traditional and modern use of the drug. Traditionally, ergot alkaloids have been used in the management of migraines and applied for oxytocic purposes during childbirth. Other applications that have been passed on to the modern world include the management of Parkinson’s disease, Alzheimer’s disease, cancer, and Type II Diabetes.
Apart from covering the relationship between ergot alkaloids and the management of disease, the article explores the biosynthesis of ergot alkaloids. The alkaloids are unified by the ergot ring. Dimethylallyltryptophan (DMAT) synthase is an enzyme that propels the biosynthetic reaction that results in the formation of the ergot ring. DMAT is involved in the committed step in the pathway towards the formation of the ergot ring. The ergot ring is tetracyclic, a factor that confers similarity to the neurotransmitters dopamine, serotonin, and noradrenaline. The resemblance of ergot alkaloids to neurotransmitters underlies their use in the management of neural-related cases such as migraines, Alzheimer’s, and Parkinson’s disease. Substitution occurs in the eighth position of Carbon in the basic ring system leading to four different groups of alkaloids. Clavine alkaloids, lysergic acid derivatives, ergopeptine alkaloids, and ergopeptam alkaloids are the four categories formed as a result of the substitution in the eighth carbon of the ring.
The article also covers the model of action of ergot alkaloids. The model of action is mediated by the neurotransmitter-like structure that means that the compounds can target the same receptors that are targeted by dopamine, serotonin, and noradrenalin. As such, ergot alkaloids will modulate 5-HT receptors, dopamine receptors, and adrenoreceptors. The action on these receptors has been shown to be instrumental in the regulation of body systems and activities as the cardiovascular functions, hormonal functions, the contraction of smooth muscles, and the control of appetite and body temperature. In the central nervous system, ergot alkaloids have been shown to combat psychiatric conditions with the aid of the metabolite LSD. In the cardiovascular system, ergot alkaloids have been implicated in causing vasoconstriction and aiding in preventing excessive bleeding. The alkaloids also affect contraction of uterine smooth muscles by mimicking the action of oxytocin.
Smart drugs have also been derived from ergot alkaloids. The three drugs handles in the article are Nicergoline, Hydrbine, and Bromocriptine. These are referred to as smart drugs as they boost the cognitive functionalities of the brain as well as increasing the memory and learning capabilities. Finally, the article deals with the different roles played by ergot alkaloids in various disease states. For instance, the article expounds on the mechanism of dihydroergotamine in the management of migraines. Apart from the function in migraine treatment, ergotamine derivatives have been used as ureotonics where the impact is to induce contraction of smooth muscles. Also, ergotamine drugs have been implicated in the synthesis of prolactin. Management of Type II Diabetes has been done for a long time using derivatives of ergot alkaloids. Bromocriptine mesylate has been in use for a long time to manage the condition. Lastly, cancer and Parkinson’s disease have as well been managed using derivatives from ergot alkaloids.
Critique
The article Ergot Alkaloids: A Review on Therapeutic Applications is an eye-opener and highly educative in through provision of basic information on the origin, scientific basis, and therapeutic applications for ergot alkaloids. The information presented in the paper is clear, and can be helpful to people doing introductory studies to the origin and therapeutic applications of ergot alkaloids. The article explores the historical perspectives of the use of ergot alkaloids and as such provides an extension for first learners on the origins in use. Also, the article is clear on the evolution in the application that the ergot alkaloid derived drugs have taken since the start of use in pharmacology.
The strength of the article is derived from the precise handling of the content. The review on the origin, scientific basis, and the therapeutic applications of the drug is done using clear subtitles that contain adequate data for learning purposes. The introduction is clear enough and gives a hint of the content of the paper by relating the structural components of ergot alkaloids to those of the neurotransmitters dopamine, serotonin, and noradrenaline. An introductory section also explains the areas that are covered in the paper, as well as the presence of a section of an expert’s opinion concerning ergot alkaloids as pharmacological agents. Thus, the introduction section is clear enough to give the reader an idea of the content covered in the body of the paper. Also, the keywords are inclusive of the main ideas that the paper covers. A reader can get more information on the concepts of the paper by exploring relevant sources for the meaning and use of the keywords “ergot alkaloids, smart drugs, ureotonic, Type II Diabetes, Migraine, Parkinson’s disease, and cancer”.
Apart from the adequately-presented introduction, the paper also draws its strength from the other sections that form the body of the paper. The ergot alkaloids biosynthesis section of the article covers the synthesis pathways adequately as explained in different sources. Also, understanding of the pharmacological action of the drug is made easier by dividing into subsections that analyze the different organ systems that are affected. As such, a reader may decide to read all or a section of interest in concerning the part of the body that is acted on the drug. On smart drugs, the author explores the applications of three ergot alkaloid derived drugs using an evidence-based strategy. Lastly, the exploration of the therapeutic applications of ergotamine-derived drugs in the management of a migraine, cancer, Type II Diabetes, Parkinson’s disease, and roles played in uterine contractions and release of the hormone prolactin.
The article, however, has a number of weaknesses that need to be handled so as to make the article better. The abstract portion of the article is sketchy, a factor that makes the paper less attractive to readers. A reader is supposed to get an adequate overview of the article before reading the body of the document. This paper does not include an introduction that covers the whole of the contents addressed. For instance, a great portion of the paper includes biosynthesis and the chemistry of ergot alkaloids which are portions not mentioned in the introduction of the document. Apart from the introduction, the author also presents a shallow conclusion. The amount of material presented in the body of the paper is much such that concluding it in a few sentences leaves out a lot of information. A characteristic shared by the introduction and the conclusion is that both are clear but do not contain adequate information for the reader.
Apart from the shallow introduction and conclusion, the paper also has a weakness for the key words mentioned in the abstract. The key words appear to be insufficient considering the amount of work covered in the content section. The author thus needs to increase the key words. For example, the broad explanation of the smart drugs Bromocriptine, Hydergine, and Nicergoline merits them to be included among the key words. Another technical challenge arises in the failure of the author to include illustrations of the processes explained in the paper. The explanation of the biosynthetic process would have been more effective with the inclusion of flow diagrams illustrating how the rings are formed and substituted to come up with the four classes of ergot alkaloids. Also, the chemistry of ergot alkaloids would have been done more sufficiently in the presence of illustrative diagrams so as to make the reader understand the mode of action in the different organ systems.
Regarding the contents of the paper, the author did a good job of expounding on the therapeutic uses of ergot alkaloids. However, it can be said that the review was not adequate. In the introduction section, the author makes it clear that is a highly poisonous compound that results in severe symptoms when consumed. However, the paper also explains that the drug was used in earlier times as an equivalent of oxytocin in childbirth. As such, it is clear to the reader that a transformation must occur for the elimination of the toxic effect. The paper does not present the transformation process and, therefore, skips an integral part. Also, the paper appears a bit shallow when presenting the therapeutic applications of ergot alkaloids. The review of literature appears to deal superficially with the results. Therapeutic applications are based on comprehensive studies that include statistical evidence to back the findings. However, the review, in this case, does not include these aspects and only makes statements derived from the used sources.
The pharmacological applications of naturally-obtained drugs need an exploration of the side effects of drugs. However, there is no mention of the side effects of all drugs mentioned in the text. The applicability of a drug as therapeutic agent relies on weighing the benefits versus the side effects. Many naturally obtained drugs have been abandoned due to toxicity, and, therefore, the author of the article needed to include the findings on the side effects of the drugs so as to merit their application. There is a lot of information on the toxicological aspects of ergot alkaloids and derivatives which the author should have reviewed.
Comments to the Author(s)
The article Ergot Alkaloids: A Review on Therapeutic Applications is a great work that can be improved through few revisions. The article is presented well regarding the structure, but the content needs to be improved. The paper is fit for learners doing introductory studies to the therapeutic applications of the widely used ergotamine alkaloids. However, a better understanding would have been aided by the inclusion of diagrammatic illustrations, especially for the biosynthesis and chemical properties of the drugs. Also, a better paper would be achieved through the incorporation of the toxicological properties of the different drugs that fall under the category of ergotamine alkaloids. Most of the drugs target critical systems such as the CNS and the cardiovascular systems, and as such provision of data on the toxicology, aspects would be good for learners and potential users.
The abstract needs to cover the content of the paper adequately. The paper also needs to be revised to eliminate a number of technical challenges that prevent perfect presentation of the same. Also, the key words need to be expanded to deal with the broad content covered in the paper. The statistical aspects of the data being reviewed need to include in the paper so as to provide adequate evidence to the readers. Additionally, the paper needs to articulate on the mechanisms for the therapeutic mechanisms in the different conditions handled as the data appears sketchy.
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