History of Tropane Alkaloids


Tropane alkaloids are plant derived organic compounds that contain a tropane ring in their chemical structure and they are among the oldest medicines known to man. Tropane alkaloids are generally secondary metabolites of these plants e.g. cocaine has insecticidal properties at naturally occurring concentrations due to potentiation of insect octopaminergic neurotransmission (Nathanson, 1993). Crude drugs and alkaloids prepared from these poisonous plants are used as an antispasmodic, sedative, anesthetic, mydriatic, etc. in therapies. 

       

















Fig. Some commercial products of tropane alkaloids

These alkaloids have been found in different plant families, Brassicaceae (Cruciferae), Convolvulaceae, Erythroxylaceae, Euphorbiaceae, Olacaceae, Proteaceae, and Rhizophoraceae, but they are best known for their occurrence in the family Solanaceae (Griffin and Lin, 2000). The family Solanaceae comprises about 100 genera and 3000 species. Particularly the genera Datura, Brugmansia, Hyoscyamus, Atropa, Scopolia, Anisodus, Przewalskia, Atropanthe, Physochlaina, Mandragora, Anthotroche,Cyphantera, and Duboisia are known as being rich in tropane alkaloids (Griffin and Lin, 2000).

  
 
 
 
 
 

Fig. Some tropane alkaloid producing plants

Tropane derivatives are among the economically most important pharmaceuticals (Rates 2001; Raskin 2002). Various pharmaceutical industries are manufacturing over 20 active pharmaceutical ingredients (APIs) containing the tropane moiety in their structures; they are applied as mydriatics, antiemetics, antispasmodics, anesthetics, and bronchodilators (Grynkiewicz and Gadzikowska, 2008). The first tropane derived commercial drug was homatropine, it was introduced by E. Merck Company as a new mydriatic in 1883.


Fig. Major applications Tropane alkaloids 

Long before the elucidation of their structures, the pharmacological properties of several tropane alkaloids were exploited e.g. atropine, which typifies the action of tropane alkaloids, causes antagonism to muscarine receptors (parasympathetic inhibition) (Cordell, 1981). These receptors are responsible for slowing of the heart rate, vasodilation, dilation of the pupil, and stimulation of secretions. The heart rate altering properties of atropine have led to its use in the initial treatment of myocardial infraction. Tropane alkaloids have also been used to treat peptic ulcers, prevent motion sickness, and as components of preanesthetic drugs.

Cocaine is perhaps the best known of all the tropane alkaloids mainly because of its use as an illicit drug; it is a powerful central nervous system stimulant and adrenergic blocking agent, and its hydrochloride salt has been used as a local and surface anesthetic in face, eye, nose, and throat surgery (Gerald, 1981). Another member, Atropine, is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.