Tropane alkaloids toxicity

Pilocarpine is a tropane alkaloid. Toxic symptoms are characterized by muscarinic effects. Toxic effects include hypersecretion of saliva, sweat, and tears contraction of the pupils of the eyes and gastric pain accompanied with nausea, vomiting, and diarrhea. Other symptoms are excitability, twitching, and lowering of blood pressure. High doses may lead to death due to respiratory failure. A lethal dose in humans is estimated within the range of 150-200 mg. 

Toxicity from tropane alkaloids often results from their effects on autonomic function. Several species of Datura are freely available, either growing in the wild or cultivated as ornamental plants, such as angel s trumpet (Datura sauveolens). Periodic outbreaks of jimsonweed use occur, when adolescents learn about the psychoactive effects of the plant and intentionally ingest it. 

The tropane alkaloids (—)-hyoscyamine and (—)-hyoscine are found in the toxic plants deadly nightshade (Atropa belladonna) and thornapple (Datura stramonium) and are widely used in medicine. Hyoscyamine, usually in the form of its racemate atropine, is used to dilate the pupil of the eye, and hyoscine is employed to control motion sickness. Both alkaloids are esters of (—)-tropic acid. 

N.A. Tropane alkaloids, hyoscyamine, hyoscine.105 Overdose can be toxic. For asthma, whooping cough, motion sickness. Externally for neuralgia and dental and rheumatic pain. 

Colchicine is a poisonous tricyclic tropane alkaloid from the autumn crocus (Colchicum autumnale) and gloriosa lily (Gloriosa superba). This alkaloid is a potent spindle fiber poison, preventing tubulin polymerization.25 Colchicine has been used as an effective anti-inflammatory drug in the treatment of gout and chronic myelocytic leukemia, but therapeutic effects are attainable at toxic or near toxic dosages. For this reason, colchicine and its analogs are primarily used as biochemical tools in the mechanistic study of new mitotic inhibitors. 

It is valuable to reiterate here that the tropane alkaloid-producing plants are all regarded as very toxic, and that since the alkaloids are rapidly absorbed into the blood stream, even via the skin, first aid must be very prompt. Initial toxicity symptoms include skin flushing with raised body temperature, mouth dryness, dilated pupils, and blurred vision. 

A variety of other tropane alkaloids have been isolated of which the most important is anatoxin-A, a highly toxic nACh-R agonist and depolarizing neuromuscular blocking agent deriving from Anabaena cyanobacterium species that can contaminate inland waters. 

Anisodus tanguticus (Zangqie), a traditional Chinese herbal medicine, contains hyoscyamine and related toxic tropane alkaloids (1). Its active ingredient anisodamine has been used to treat snakebite (2). 

Mandragora (mandrake) species contain toxic tropane alkaloids, such as hyoscyamine and/or scopolamine. 

Alkaloids are classified according to their heterocyclic rings. For example, cocaine, a central nervous system stimulant, and atropine, a muscle relaxant, are examples of the tropane alkaloids in which a nitrogen appears in a bridge of a seven-membered ring structure. Nicotine, the addictive and toxic component of tobacco, is an example of the pyridine alkaloids in which a nitrogen appears as a member of a six atom aromatic ring. (Nicotine is an effective insecticide.) The addictive... 

Young children are especially exposed to the toxic effects of tropane alkaloids. Serious intoxication may occur by ingestion of berries of Atropa belladonna. Furthermore, poisoning from the ingestion and the smoking of jimsonweed or thorn apple is not infrequent. The toxicity symptoms which can occur are skin rash, flushing of skin, dryness of mouth, difficult urination, eye pain, blurred vision and sensitivity to light. 

Quaternary derivatives of the tropane alkaloids are curare-like the tro-pinium salts are very weak, but the atropinium salts are fairly effective. A -Methylatropinium bromide is effective in frogs in doses of 6-10 mg./kg. and is very non-toxic. Recently, decamethylenebisatropinium diiodide has been shown to be 140 times as potent in frogs as fV-methylatropinium salts and twice as potent as d-tubocurarine (115, 116). 

Although atropine is a known antidote against several toxic substances, its overdose can cause severe poisoning. As with other tropane alkaloids, atropine competitively blocks muscarinic acetylcholine receptor sites. This results in dilation of the pupil of the eye (mydriatic effect), dryness of the mucous membranes, especially of the mouth, and inhibition of activity of sweat glands (parasympatholytic action). At toxic doses, it causes palpitation, speech disturbance. 

C HjjNOj, Mr 289.37, needles, mp, 106-108 °C, [ain -22° (50% C2H5OH/H2O), A tropane alkaloid form numerous Solanaceae genera such as, e.g. Atropa (deadly nightshade). Datura (thorn apple), Du-boisia, Hyoscyamus (henbane), and Scopolia (banewort). H. racemizes slowly in alcoholic solution, rapidly in alkaline and acidic solutions and in molten state to atropine. It has the same effects on the central nervous system as atropine and a twice as strong toxic effect on the peripheral nervous system [LD50 (mouse i. V.) 95 mg/kg]. Symptoms of poisoning include dry mouth and throat. For isolation from cell cultures, see Lit. For biosynthesis, see tropane alkaloids. 

Todd FG, Stermitz FR, SchultheisP, Knight AP, Traub-Daigatz J (1995) Tropane alkaloids and toxicity of Convolvulus arvensis. Phytochemistry 39(2) 301-303... 

Tropane alkaloids, e.g., L-hyoscyamine and L-scopolamine are toxic to most animals (see above) and therefore are of ecological significance in repelling poten-... 

Tropane alkaloids of the structural types T1 - T4, T7-C, and T7-D (subclass B ester alkaloids of lower or unknown toxicity with acid residue other than tropic acid and its derivatives)... 

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