ABOUT AMINES AND ALKALOIDS

What are amins and alkaloids

An amine contains a nitrogen atom that is bounded to at least one carbon atom, and where the other bindings go to either a hydrogen atom or other carbon atoms.

Complex amins are usully called alkaloids. In alkaloids the nitrogen atom has at least two bindings to carbon atoms, and at least one of these is the beginning of some complex chain or ring structure. The nitrogen atoms can take up a proton from an acid, and thus these compounds act as a base. Because of this chemical property, amins and alkaloids are powerful actors in the human body. Many are potent poisons, some are neurotransmotters or hormones. Many of them are used in medicine to cure diseases, to alleviate symptoms or modify physiological, mechanisms. Alkaloids most often has their effect in the nervous system.

Alkaloids are usually derivatives of amino acids, and many have a bitter taste. They are found as secondary metabolites in plants (e.g. potatoes and tomatoes), animals (e.g. shellfish) and fungi. Many alkaloids can be purified from crude extracts by acid-base extraction.
 

Effects and uses of alkaloids

Here are some alkaloids listed according to their main mediacal or biological effects. Some alkaloids have several effects and are therefore listed more than once.

Hormons or neurotransmitter substances in the body or precursors for these: Dopamine, choline, serotonine, acetylcholine

Strong tasting elements in food or spices: Piperine

Acting against inflammation, fever or pain: Quinine

Anti-microbial acting used to cure infections: Quinine (against malaria)

Very poisenous alkaloids: Sanguinarine, muscarine, solanine, coniine, cytisine, aconitine, neurine

Very poisonous alkaloids that are used in very small amounts in some medicines to improve heart function, relaxe muscles or for other puposes: Strychnine, sanguinarine, atropine, scopalamine

Cell poisons, disturbing cell division, used as cytostatica to kill cancer cells or to help cure other diseases with exaggerated cell proliferation: Vinblastine, vincristine.

Nervous stimulants that effects both emotions and various organs: Yohimbine

Central nervous system stimulants enjoyed in  food and beverages. Some are used to increase metabolism and help against over-weight: Caffeine, theobromine, theophylline, guaranine

Central nervous stimulaqting and addictive narcotics. Some are enjoyed legally or illegally, and some have uses in medicine.  Ephedrine,  amphetamine, nicotine, thebaine

Anti-depressants, monoamine oxidase inhibitors:  Harmine, harmaline

Halusinogenic narcotics: Mescaline, scopalamine, harmaline, dymetyltryptamine, psilocybine, lysergic acid, lysergic acid diethylamide (LSD)

Sedating and addictive narcotics that are also used medicinally as analgesics (pain relievers) or anaesthetics; Morphine, thebaine, papaverine, narcotine,  berberine, scoplamine

Sedating agents with antipsychotic or other specific actions: Reserpine.

Sedating or muscle relaxant alkaloids, used against cough and other medical purposes: Codeine, noscapine

Alkaloids with various physiological stimulating or relaxing effects upon smooth muscles and glands, used in medical treatments: Pilocarpine, Ergoline (migraine treatment)

Chemical grouping of alkaloids

Alkaloids kan be grouped chemically according to some chemical compound they resamble, and that they often are produced from by plants animals or pharmacological industry.

Pyridine group: piperine, coniine, trigonelline, arecaidine, guvacine, pilocarpine, cytisine, nicotine, sparteine, pelletierine.
Pyrrolidine group: hygrine, cuscohygrine, nicotine
Tropane group: atropine, cocaine, ecgonine, scopolamine
Quinoline group: quinine, quinidine, dihydroquinine, dihydroquinidine, strychnine, brucine, veratrine, cevadine
Isoquinoline group: The opium alkaloids (morphine, codeine, papaverine, narcotine, sanguinarine, narceine,berberine)
Phenethylamine group: mescaline, ephedrine, dopamine, amphetamine
Indole group:
Tryptamines: DMT, N-methyltryptamine, psilocybin, serotonin
Ergolines: the ergot alkaloids (ergine, ergotamine, lysergic acid, etc.)
Beta-carbolines: harmine, harmaline, yohimbine, reserpine, emetine
Purine group:
Xanthines: caffeine, theobromine, theophylline
Terpenoid group:
Aconite alkaloids: aconitine
Steroids: solanine, samandaris (quaternary ammonium compounds): muscarine, choline, neurine
Vinca alkaloids: vinblastine, vincristine.

Physical properties of alkaloids

Molecular weight 100-900
Those without oxygen atoms in the structure are usually liquid at ordinary temperature (e.g. nicotine, sparteine, coniine)
Those with oxygen atoms are crystalline (e.g. berberine)
Optically active
Basicity depends on the availability of lone pairs of electrons on the N atom & the type of heterocycle and substituents.
Ability to form salts with mineral acids (e.g. with HCl, H2SO4, HNO3) or organic acids (e.g. tartrates, sulfamates, maleates)

(Most of this information is compiled form wikipedia.org)

ABOUT SOME SPECIFIC ALKALOIDS

Piperine - the tasting element in pepper

Piperine is the alkaloid responsible for the pungency of black pepper along with chavicine (an isomer of piperine). It has also been used in some forms of traditional medicine and as an insecticide.

The pungency caused by capsaicin and piperidine is caused by activation of the heat and acidity sensing TRPV ion channel TRPV1 on nociceptors (pain sensing nerve cells).

Piperine has also been found to inhibit human CYP3A4 and P-glycoprotein, enzymes important for the metabolism and transport of xenobiotics and metabolites (PMID 12130727). In animal studies, piperine also inhibited other enzymes important in drug metabolism (PMID 3917507, PMID 8347144). By inhibiting drug metabolism, piperine may increase the bioavailability of various compounds. Notably, piperine may enhance bioavailability of curcumin by 2000% in humans (PMID 9619120).

Due to its effects on drug metabolism, piperine should be taken cautiously (if at all) by individuals taking other medications.

Dopamine - a neurotransmitter and local brain hormone

Dopamine is a phenethylamine naturally produced by the human body. In the brain, dopamine functions as a neurotransmitter, activating the five types of dopamine receptor - D1, D2, D3, D4 and D5, and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra.

Dopamine is also a neurohormone released by the hypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary.

Dopamine can be supplied as a medication that acts on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure. However, since dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system. To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease and Dopa-Responsive Dystonia, L-DOPA (levodopa), which is the precursor of dopamine, can be given because it can cross the blood-brain barrier.
 

Serotonine - an important neurotransmitter

Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract of animals including humans. Serotonin is also found in many mushrooms and plants, including fruits and vegetables.

In the central nervous system, serotonin is believed to play an important role in the regulation of anger, aggression, body temperature, mood, sleep, vomiting, sexuality, and appetite. Low levels of serotonin may be associated with several disorders, namely increase in aggressive and angry behaviors, clinical depression, obsessive-compulsive disorder (OCD), migraine, irritable bowel syndrome, tinnitus, fibromyalgia, bipolar disorder, anxiety disorders[citation needed] and intense religious experiences[1]. If neurons of the brainstem that make serotonin—serotonergic neurons—are abnormal, there is a risk of sudden infant death syndrome (SIDS).

Coline - an important nutrient

Choline is an organic compound, classified as an essential nutrient and usually grouped within the Vitamin B complex. This natural amine is found in the lipids that make up cell membranes and in the neurotransmitter acetylcholine. Adequate intakes  for this micronutrient of between 425 to 550 milligrams daily, for adults, have been established by the Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences.

Coline is used in many alternative drugs to support the function of the nervous system, and the ability of tissue to heal from damage.

Acetylcoline - an important neurotransmittor

Acetylcholine is an ester of acetic acid and choline with chemical formula CH3COOCH2CH2N+(CH3)3. This structure is reflected in the systematic name, 2-acetoxy-N,N,N-trimethylethanaminium.

The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. It is a chemical transmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in many organisms including humans. Acetylcholine is the neurotransmitter in all autonomic ganglia. In layman's terms, it is a chemical that allows neurons to communicate with each other within humans and other organisms.

Quinine - treating fever, inflammation, pain and malaria

Quinine is a natural white crystalline alkaloid having antipyretic (fever-reducing), antimalarial, analgesic (painkilling), and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine.

Quinine was the first effective cure for falciparum malaria, appearing in therapeutics in the 17th century. It remained the antimalarial drug of choice until the 1940s, when other drugs took over. Since then, many effective antimalarials have been introduced, although quinine is still used to treat the disease in certain critical situations. Quinine is available with a prescription in the United States. Quinine is also used to treat nocturnal leg cramps and arthritis, and there have been attempts (with limited success) to treat prion diseases. It was once a popular heroin adulterant.
 

Pilocarpine - a parasympatetic antagonist

Pilocarpine is a muscarinic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It acts as a muscarinic receptor agonist in the parasympathetic nervous system.

Pilocarpine has been used in the treatment of chronic open-angle glaucoma and acute angle-closure glaucoma for over 100 years.[1] It acts on a subtype of muscarinic receptor (M3) found on the iris sphincter muscle, causing the muscle to contract and produce miosis. This opens the trabecular meshwork through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the eye to decrease intraocular pressure.

Pilocarpine is also used to treat dry mouth (xerostomia). Pilocarpine stimulates the secretion of large amounts of saliva and sweat. It may also cause hypotension and bradycardia in the cardiovascular system, and bronchospasm and increased bronchial secretion in the lungs due to its non-selective muscarinic action.

Pilocarpine is used to stimulate sweat glands in a sweat test to measure the concentration of chloride and sodium that is excreted in sweat. It is used to diagnose cystic fibrosis (CF).

 

Papaverine - some specific medical uses

Papaverine is approved to treat spasms of the gastointestinal tract, bile ducts and ureter and for use as a cerebral and coronary vasodilator in subarachnoid hemorrhage (combined with balloon angioplasty) and coronary artery bypass surgery. Papaverine may also be used as a smooth muscle relaxant in microsurgery where it is applied directly to blood vessels.

Noscapine - some specific medical uses

Noscapine is used as a cough suppressing agent.

Noscapine is currently under investigation for use in the treatment of several cancers and . In cancer treatment, noscapine appears to interfere with microtubule function, and thus the division of cancer cells in a way similar to the taxanes. Early studies in treatment of prostate cancer are very promising.  Studies are currently underway to assess the effectiveness of this drug in cancer and stroke treatment. Noscapine is non-addictive, widely available, has a low side-effect incidence, and is easily administered orally, thus it has great potential for use, especially in developing countries.

Noscapine is also investigated for effectiveness against hypoxic ischemia in stroke patients in stroke treatment. In stroke patients, noscapine blocks the bradykinine b-2 receptors. A 2003 study in Iran showed a dramatic decrease in mortality in patients treated with noscapine.

Noscapine formula - An example of an alkaloid chemical structure.
 

Nicotine - possible medical uses

Smoking is dangerous to the health. However, smokers have certain health benefits in specific situations, probably effected by nicotine. Nicotine itself may therefor be uses to help cure certain diseases, when admistered without smoking. However conclusive areas to use nicotine as a cure against diseases are not yet established.

For instance, recent studies suggest that smokers require less frequent repeated revascularization after percutaneous coronary intervention (PCI). Risk of ulcerative colitis has been frequently shown to be reduced by smokers on a dose-dependent basis. The effect is eliminated if the individual stops smoking. Smoking also appears to interfere with development of Kaposi's sarcoma,  breast cancer among women carrying the very high risk BRCA gene, preeclampsia, and atopic disorders such as allergic asthma. A plausible mechanism of action in these cases may be nicotine acting as an anti-inflammatory agent, and interfering with the inflammation-related disease process, as nicotine has vasoconstrictive effects.

With regard to neurological diseases, a large body of evidence suggests that the risks of Parkinson's disease or Alzheimer's disease might be twice as high for non-smokers than for smokers. Many such papers regarding Alzheimer's disease and Parkinson's Disease have been published. A plausible mechanism of action in these cases may be the effect of nicotine, a cholinergic stimulant, in decreasing the levels of acetylcholine in the smoker's brain. Parkinson's disease occurs when the effect of dopamine is less than that of acetylcholine.

Recent studies have indicated that nicotine can be used to help adults suffering from Autosomal dominant nocturnal frontal lobe epilepsy. The same areas that cause seizures in that form of epilepsy are also responsible for processing nicotine in the brain.

Nicotine and its metabolites are being researched for the treatment of a number of disorders, including ADHD and Parkinson's Disease.

The therapeutic use of nicotine as a means of appetite-control and to promote weight loss is anecdotally supported by many ex-smokers who claim to put on weight after quitting. However studies of nicotine in mice  suggests it may play a role in weight-loss that is independent of appetite. And studies involving the elderly suggest that nicotine affects not only weight loss, but also prevents some weight gain.
 

(Most of this information is compiled form wikipedia.org)