Mandrake is the common name for members of the plant genus Mandragora, particularly the species Mandragora officinarum, belonging to the nightshades family Solanacea , including Mandragora officinarum L. and Mandragora vernalisBertol (sometimes called Atropa mandragora).
Because mandrake contains deliriant hallucinogenic tropane alkaloids such as atropine, scopolamine, apoatropine, and hyoscyamine, and the roots sometimes contain bifurcations causing them to resemble human figures, their roots have long been used in magic rituals
Mandrake plant, 2014
Mandragora, Year introduced: 2002, 1963-1996
Genus: Mandragora L.
- in the past…
The scent of the mandrake fruit was reputed to alleviate headaches and insomnia. Hippocras noted that a small dose would relieve anxiety and the deepest depression. If drunk its hypnotic properties allowed amputation or cauterization. It was also used as an aphrodisiac and cure for sterility.
This plant dates back thousands of years and it was used in medicine as a narcotic before surgery, but also as an emetic and as antidote for snakebites.
Although anaesthesia was discovered in 1846, initial attempts at surgical anesthesia began many centuries ago, with the plants of antiquity. The mandragora, or mandrake, was used as a sedative and to induce pain relief for surgical procedures. It has been depicted in tablets and friezes since the 16th century before the common era. The Romans used the mandrake for surgery. The Arabs translated the scientific work of the Ancients and expanded on their knowledge. They developed the SpongiaSomnifera , which contained the juice of the mandrake plant. After the fall of the Islamic cities of Europe to the Christians, scientific work was translated into Latin and the SpongiaSomnifera was used in Europe until the discovery of the use of ether for surgical anesthesia.
Neurological stamp, 2014
Accidental Poisoning after Ingestion of “Aphrodisiac” Berries: Diagnosis by Analytical Toxicology, 2012(11)00299-X/abstract
Some observations on early military anaesthesia, 2006
Special article: mandragora: anesthetic of the ancients, 2012
- modern research
More modern research , including within the realm of homeopathy, has shown that the effects of mandrake are very similar to Belladonna , including the following clinical symptoms: dry mouth, nose, and throat; muscular atony; an increase in pulse frequency; eye issues such as farsightedness and pupil dilation; and the immediate short-term memory loss.
Modern accounts with mandrake wine describe a more enjoyable experience, including sensations of pleasure coursing through the body, a mild euphoria, and dream activity, with a greater frequency of sexually oriented dreams. Slight cranial pressure and visual hallucinations may occur. An increased proclivity towards music, particularly rhythm, has been noted, as has a diminished sense of ego.
Atropine poisoning by Mandragora autumnalis. A report of 15 cases, 1990
- what mandragora is made of?
The alkaloid chemicals contained in the root include atropine, scopolamine, and hyoscyamine. These chemicals are anticholinergics, hallucinogens, and hypnotics.
Anticholinergic properties can lead to asphyxiation. Ingesting mandrake root is likely to have other adverse effects such as vomiting and diarrhea. The alkaloid concentration varies between plant samples, and accidental poisoning is likely to occur.
ACTIVE MOLECULES DESCRIPTION
c) medical uses
c) medical uses
c) medical uses
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna), Jimson weed (Daturastramonium), mandrake (Mandragoraofficinarum) and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects.
In general, atropine counters the "rest and digest" activity of glands regulated by the parasympathetic nervous system . This occurs because atropine is a competitive antagonist of themuscarinic acetylcholine receptors (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system). Atropine dilates the pupils, increases heart rate, and reduces salivation and other secretions.
The biosynthesis of Atropine starting from L-Phenyalanine first undergoes a transamination forming Phenypyruvic Acid which is then reduced to Phenyl-lactic Acid. Coenzyme A then couples Phenyl-Lactic Acid with Tropine forming Littorine, which then undergoes a radical rearrangement initiated with a P450 enzime forming Hyoscyamine Aldehyde. A dehydrogenase then reduces the aldehyde to a primary alcohol making Hyoscyamine, which upon racemization forms atropine.
c) medical uses
It is a competitive antagonist for the muscarinic acetylcholine receptor types M1, M2, M3, M4 and M5. It is classified as an anticholinergic drug (parasympatholytic).
Working as a nonselective muscarinic acetylcholinergic antagonist, atropine increases firing of the sinoatrial node (SA) and conduction through the atrioventricular node (AV) of the heart, opposes the actions of the vagus nerve , blocks acetylcholine receptor sites, and decreases bronchial secretions.
Topical atropine is used to temporarily paralyze the accommodation reflex , and as a mydriatic, to dilate the pupils. It is preferred as an aid to ophthalmic examination.
Injections of atropine are used in the treatment of bradycardia (an extremely low heart rate). Atropine blocks the action of the vagus nerve, a part of the parasympathetic system of the heart whose main action is to decrease heart rate.
Secretions and bronchoconstriction
Atropine's actions on the parasympathetic nervous system inhibit salivary and mucus glands. The drug may also inhibit sweating via the sympathetic nervous system. This can be useful in treating hyperhidrosis
Side-effects and overdose
Adverse reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, dry mouth and potentially extreme confusion, dissociative hallucinations and excitation especially amongst the elderly. These latter effects are because atropine is able to cross the blood–brain barrier . Because of the hallucinogenic properties, some have used the drugrecreationally, though this is potentially dangerous and often unpleasant.
In overdoses, atropine is poisonous.
A common mnemonic used to describe the physiologic manifestations of atropine overdose is: "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter". These associations reflect the specific changes of warm, dry skin from decreased sweating, blurry vision, decreased sweating/lacrimation, vasodilation, and central nervous system effects on muscarinic receptors, type 4 and 5. This set of symptoms is known as anticholinergic toxidrome.
Hyoscyamine (also known as daturine) is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family. It is the levorotary isomer of atropine and thus sometimes known as levo-atropine. Hyoscyamine should not be confused with hyoscine, an older alternate name for the related nightshade-derived anticholinergic scopolamine for which it is the precursor.
At comparable doses, hyoscyamine has 98 per cent of the anticholinergic power of atropine. The other major belladonna-derived drug scopolaminehas 92 per cent of the antimuscarinic potency of atropine.
As hyoscyamine is a direct precursor in the plant biosynthesis of scopolamine, it is produced via the same metabolic pathway.
The biosynthesis of scopolamine begins with the decarboxylation of L-ornithine to putrescine by ornithine decarboxylase. Putrescine is methylated to N-methylputrescinebyputrescine N-methyltransferase.
A putrescine oxidase that specifically recognizes methylated purtrescinecatalizes the deamination of this compound to 4-methylaminobutanal which then undergoes a spontaneous ring formation to N-Methyl-pyrroliumcation. In the next step, the pyrroliumcation condenses with acetoacetic acid yielding hygrine. No enzmyatic activity could be demonstrated that catalyzes this reaction. Hygrine further rearranges to tropinone.
Subsequently, Tropinone reductase Iconverts tropinone to tropine which condenses with phenylalanine-derived phenyllactate to littorine. A cytochrome P450 classified as Cyp80F1 oxidizes and rearranges littorine to hyoscyamine aldehyde.
c) medical uses
Hyoscyamine is used to provide symptomatic relief to various gastrointestinal disorders including spasms, peptic ulcers, irritable bowel syndrome, diverticulitis, pancreatitis, colic and cystitis. It has also been used to relieve some heart problems, control some of the symptoms of Parkinson's disease's_disease , as well as for control of respiratory secretions in palliative care. It may be useful in pain control for neuropathic pain treated with opioids as it increases the level of analgesia obtained. Several mechanisms are thought to contribute to this effect. When hyoscyamine is used along with opioids or other anti-peristaltic agents, measures to prevent constipation are especially important given the risk of paralytic ileus .
Side effects include dry mouth and throat, eye pain, blurred vision, restlessness, dizziness, arrhythmia, flushing, and faintness. An overdose will cause headache, nausea, vomiting, and central nervous system symptoms including disorientation, hallucinations, euphoria, sexual arousal, short-term memory loss, and possible coma in extreme cases. The euphoric and sexual effects are stronger than those of atropine but weaker than those of scopolamine.
Scopolamine also known as levo-duboisine, hyoscine or burundanga, sold as Scopoderm, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants. Scopolamine exerts its effects by acting as a competitive antagonist at muscarinic acetylcholine receptors, specifically M1 receptors; it is thus classified as an anticholinergic, antimuscarinicdrug.
The biosynthesis of scopolamine begins with the decarboxylation of L-ornithine to putrescine by ornithine decarboxylase. Putrescine is methylated to N-methylputrescine by putrescine N-methyltransferase. A putrescine oxidase that specifically recognizes methylated purtrescinecatalizes the deamination of this compound to 4-methylaminobutanal which then undergoes a spontanous ring formation to N-Methyl-pyrroliumcation. In the next step, the pyrroliumcation condenses with acetoacetic acid yielding hygrine. No enzmyatic activity could be demonstrated that catalyzes this reaction. Hygrine further rearranges to tropinone. Subsequently, Tropinone reductase I converts tropinone to tropine which condenses with phenylalanine-derived phenyllactate to littorine. A cytochrome P450 oxidizes and rearranges littorine to hyoscyamine aldehyde. In the final step, hyoscyamine undergoes epoxidation catalyzed by 6beta-hydroxyhyoscyamine epoxidaseyielding scopolamine.
c) medical uses
Its use in medicine is relatively limited, with its chief uses being in the treatment of motion sickness and postoperative nausea and vomiting.
Pharmaceutic form Buscopan
The N -butyl bromide derivative of scopolamine, available commercially as Buscopan, is commonly used as an antispasmotic
Buscopan, which contains N-butyl scopolammonium bromide (BSB), is indicated for the relief of abdominal discomfort, pain, and acute colic. As a quaternary ammonium compound with low lipid solubility, BSB cannot pass the blood-brain barrier easily and only rarely causes the central nervous system side effects associated with atropine and scopolamine.
PHARMACOKINETICS AND TOXICITY
Undesirable effects, overdose and Pharmacokinetic properties
The alkaloids competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. The parasympatholytic scopolamine, structurally very similar to atropine (racemate of hyoscyamine), is used in conditions requiring decreased parasympathetic activity.
Hyoscine (scopolamine) shows similar binding affinities to all of the five known muscarinic receptor sub-types.
Muscarinic acetylcholine receptors mediate diverse physiological functions. At present, five receptor subtypes (*M1 - M5*) have been identified. The odd-numbered receptors (M1, M3, and M5) are preferentially coupled to Gq/11 and activate phospholipase C, which initiates the phosphatidylinositol trisphosphate cascade leading to intracellular Ca2+ mobilization and activation of protein kinase C. On the other hand, the even-numbered receptors (M2 and M4) are coupled to Gi/o, and inhibit adenylyl cyclase activity. They also activate G protein-gated potassium channels, which leads to hyperpolarization of the plasma membrane in different excitable cells. Individual members of the family are expressed in an overlapping fashion in various tissues and cell types. Muscarinic receptors have been emerging as an important therapeutic target for various diseases, including dry mouth, incontinence and chronic obstructive pulmonary disease.
Atropine binds these receptors and inhibit their activaction by acetylcholine, the systemic effect of this action is the inhibition of the parasympathetic nervous system.
The International Journal of Plant Chemistry, Plant Biochemistry and Molecular Biology, 2014
The presented review gives us the present state of knowledge in the chemistry of all different parts of mandragora plant. As we can see, the literature in this area is not abundant, but its contribution is significant. The chemical principle of its “magic” (hallucinogenic and poisonous) properties is today well known, but to understand its “aphrodisiac” (“love”) properties, still some more analytical work would be done. Further research can bring new and unexpected information.