Isoquinoline Alkaloids

Opium Alkaloids

• Many alkaloids have been identified in opium latex (opiates) - maybe as many as 50.

• Morphine and codeine are the most importantMorphine first alkaloid identified from any plant in

1806 and the pain relieving properties soon recognized

• Morphine (like raw opium) is strongly addictive and because of this its general medical use declined in 20th century

• Still drug of choice for cases of severe pain

Opium Poppy: Papaver somniferum

• Member of the Papaveraceae, poppy family• Large showy annual with conspicuous flowers

(white, pink, red, purple)• Fruit is a capsule that produces latex with

several potent alkaloids• Latex is collected from cut capsules (latex

oozes out and dries – dried latex scraped off) - dried latex called opium

Fresh capsule of opium poppy Cut capsule showing latex exuding from cut

Morphine

O

HOH

NH

CH3

HO1

23

4

5

6

7

8

9

10

11

12

1314

15 16

Morphine (Astramorph)

HO- Group is needed for activity

HO- Group not important to activity

Morphine is primarily used to treat both acute and chronic severe pain. It is also used for pain due to myocardial infarction and for labor pains. There are however concerns that morphine may increase mortality in the setting of non ST elevation myocardial infarction. Morphine has also traditionally been used in the treatment of acute pulmonary edema. A 2006 review however found little evidence to support this practice.Immediate release morphine is beneficial in reducing the symptom of acute shortness of breath due to both cancer and non-cancer causes. In the setting of breathlessness at rest or on minimal exertion from conditions such as advanced cancer or end-stage cardio-respiratory diseases, regular, low-dose sustained release morphine significantly reduces breathlessness safely, with its benefits maintained over time.Its duration of analgesia is about 3–4 hours when administered via the intravenous, subcutaneous, or intramuscular route and 3–6 hours when given by mouth. Morphine is also used in slow release formulations for opiate substitution therapy (OST) in Austria, Bulgaria, and Slovenia, for addicts who cannot tolerate the side effects of using either methadone or buprenorphine, or for addicts who are "not held" by buprenorphine or methadone. It is used for OST in many parts of Europe although on a limited basis

Codeine

Codeine or 3-methylmorphine (a naturally occurring methylated morphine) is an opiate used for its analgesic, antitussive, antidiarrheal, antihypertensive, anxiolytic, antidepressant, sedative and hypnotic properties. It is also used to suppress premature labor contractions, myocardial infarction, and has many other potential and indicated uses. It is often sold as a salt in the form of either codeine sulfate or codeine phosphate in the United States and Canada; codeine hydrochloride is more common worldwide and the citrate, hydroiodide, hydrobromide, tartrate, and other salts are also seen.Codeine is the second-most predominant alkaloid in opium, at up to three percent. Although codeine can be extracted from natural sources, a semi-synthetic process is the primary source of codeine for pharmaceutical use. It is considered the prototype of the weak to midrange opioids (tramadol, dextropropoxyphene, dihydrocodeine, hydrocodone, oxycodone).

Heroin

diacetylmorphine or morphine diacetate, also known as diamorphine

Heroin is an opioid analgesic originally synthesized by C.R. Alder Wright in 1874 by adding two acetyl groups to the molecule morphine, which is found naturally in the opium poppy. It is the 3,6-diacetyl ester of morphine. Heroin itself is an inactive drug, but when inserted into the body, it converts into morphine.Illicit (( مشروع heroin is sometimes available in freebase form. Because غيرof its lower boiling point, the freebase form of heroin is also smokable. It is prevalent in heroin coming from Afghanistan, which in 2004 produced roughly 87% of the world supply in illicit raw opium. However, the production rate in Mexico has risen sixfold from 2007 to 2011, changing that percentage and placing Mexico as the second largest opium producer in the world.As with other opioids, diacetylmorphine is used as both an analgesic and a recreational drug. Frequent and regular administration is associated with tolerance and physical dependence. Internationally, diacetylmorphine is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs. It is illegal to manufacture, possess, or sell diacetylmorphine without a license in almost every country, except the UK and Switzerland

Other Isoquinoline Alkaloids

Emetine

Emetine

Emetine is a drug used as both an anti-protozoal and to induce vomiting. It is produced from the ipecac root.

Early use of emetine was in the form of oral administration of the extract of ipecac root, or ipecacuanha. This extract was originally thought to contain only one alkaloid, emetine, but was found to contain several, including cephaeline, psychotrine and others. Although this therapy was reportedly successful, the extract caused vomiting in many patients which reduced its utility. In some cases, it was given with opioids to reduce nausea. Other suggestions to reduce nausea involved coating the drug to allow it to be released after digestion in the stomach.

Test for emetine

Mix 0.5g powdered herb with 20ml HCL and 5ml water.

FilterTo 2ml filtrate add 0.01g potassium chlorate

Result: if emetine is present, a yellow colour appears. After standing for 1hr, changes to red

Carapichea Ipecacuanha

Carapichea ipecacuanha is a flowering plant native to Brazil. Traditionally its roots were used to make a powerful emetic to induce vomiting at times of poisoning. Until recent times, it was still used within hospitals and homes for this purpose

Berberine

Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis [e.g. Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense (Amur cork tree), Coptis chinensis (Chinese goldthread or Huang Lian Su), Tinospora cordifolia, Argemone mexicana (prickly poppy), and Eschscholzia californica (Californian poppy). Berberine is usually found in the roots, rhizomes, stems, and bark. Due to Berberine's strong yellow color, Berberis species were used to dye wool, leather and wood. Wool is still today dyed with berberine in northern India. Under ultraviolet light, berberine shows a strong yellow fluorescence, so it is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 75160. As a traditional medicine or dietary supplement, berberine has shown some activity against fungal infections, Candida albicans, yeast, parasites, and bacterial/viral infections. Berberine seems to exert synergistic effects with fluconazole even in drug-resistant C. albicans infections

(Berberidaceae (Berberis aquifolium

Physostigmine ( Eserine) Uses

• Physostigmine is used to treat glaucoma, Alzheimer's disease, and delayed gastric emptying. It has been shown to improve short term memory. Recently, it has begun to be used in the treatment of orthostatic hypotension.

• Because it is a tertiary amine, it can cross the blood–brain barrier, and physostigmine salicylate is used to treat the central nervous system effects of atropine, scopolamine, and other anticholinergic drug overdoses.

• Physostigmine is the antidote of choice for Datura stramonium poisoning. It is also an antidote for Atropa belladonna poisoning, the same as for atropine.

Calabar beanThe Calabar bean is the seed of a leguminous plant, Physostigma

venenosum, a native of tropical Africa, poisonous to humans. It derives the first part of its scientific name from a curious beak-like appendage at the end of the stigma, in the centre of the flower; this appendage, though solid, was supposed to be hollow.

Strychnos nux-vomica• The strychnine tree (Strychnos nux-vomica L.) also known as nux

vomica, poison nut, and quaker buttons, is a deciduous tree native to India, and southeast Asia. It is a medium-sized tree in the family Loganiaceae that grows in open habitats. Its leaves are ovate and 2–3.5 inches (5.1–8.9 cm) in size.

• It is a major source of the highly poisonous, intensely bitter alkaloids strychnine and brucine, derived from the seeds inside the tree's round, green to orange fruit. The seeds contain approximately 1.5% strychnine, and the dried blossoms contain 1.0%. However, the tree's bark also contains brucine and other poisonous compounds.

• The use of strychnine is highly regulated in many countries, and is mostly used in baits to kill feral mammals, including wild dogs, foxes, and rodents. Most accidental poisoning is by breathing in the powder or by absorption through the skin

Rauwolfia serpentina

Vinca ((Catharanthus roseus

معجل للوالدة

الشقيقة

) Ryeألجاودر)

• Rye (Secale cereale) is a grass grown extensively as a grain, a cover crop and as a forage crop. It is a member of the wheat tribe (Triticeae) and is closely related to barley (Hordeum) and wheat (Triticum). Rye grain is used for flour, rye bread, rye beer, crisp bread, some whiskeys, some vodkas, and animal fodder. It can also be eaten whole, either as boiled rye berries, or by being rolled, similar to rolled oats.

• Rye is a cereal grain and should not be confused with ryegrass, which is used for lawns, pasture, and hay for livestock

Rye