Cocaine, development from natural

The traditional method of drag development, at least in this century, has been to develop leads by first using, and then by isolating and identifying, the active chemical constituents from natural products, some of which may have been medicinally in use since antiquity. With the advent of modem organic chemistry some of these purified compounds were used directly (e.g., morphine, cocaine, atropine, quinine), and, once their chemical structures were ascertained, they became leads for hoped-for chemical modifications to achieve improved efficacy, less toxicity, or, at least, higher potency (e.g., dihydromorphinone, homatropine, acetylsalicylic acid). 

A frequently cited example of an important natural-product-derived drag is the neuromuscular blocker d-tubocurarine, derived from the South American plant curare, which was used by South American Indians as an arrow poison (see Chapter 26). Tubocurarine led to the development of decamethonium, which, although structurally dissimilar to tubocurarine, was nevertheless synthesized based on the then prevalent presumption that tubocurarine contained two quaternary nitrogens. Similarly, synthetic local anesthetics, such as lidocaine, benzocaine, and dibucaine, were synthesized to mimic the nerve-blocking effect of cocaine, a natural alkaloid obtained from the leaves of Coca eroxylum, but without the adverse side effects that have led to its abuse. 

In 1995, scientists at Scripps Research Institute reported the development of a vaccine that elicits antibodies to cocaine. The nature of the antigen is a cocaine analog bound covalently to a protein with a Monty Python-like name, keyhole limpet hemocyanin. Administration of the complex resulted in a reduction of the psychoactive response to subsequently administered cocaine. In experiments in rats, the antibodies bound cocaine in the bloodstream and prevented the drug from crossing the blood-brain barrier. A potential clinical application would be to immunize cocaine abusers... 

These natural reward centers have developed over the course of evolution to reinforce useful behaviors (e.g., pleasure, sexual satisfaction, eating, and drinking). It is believed that drugs such as cocaine and amphetamine directly stimulate these centers, while opiates free the pathways from inhibitory control. Nicotine, on the other hand, reaches the brain in as little as 10-20 seconds, where it stimulates nicotine receptors to cause dopaminergic neurons to release large quantities of dopamine. After a few hours, dopamine levels decline, causing withdrawal symptoms to readily appear (e.g., anxiety, irritability, and inattentiveness). When cigarette smokers say they need a smoke to steady their nerves, what they really mean is that they have to contend with nicotine withdrawal. 

Numerous applications have been developed for a wide variety of compounds from different matrices, but surprisingly, only a few reviews dedicated to the extraction of medicinal plants have been pubhshed in the last few years [37-39]. ASE of cocaine and benzoylecgonine from coca leaves has been reported by Brachet et al. [40]. The influence of several extraction parameters such as the nature of the extracting solvent, the addition of alkaline substances, the pressure, the temperature, the extraction time, and the sample granulometry on cocaine recovery was systematically investigated. Methanol was fotmd to be the most suitable solvent. Critical parameters were found to be pressure, temperature, and extraction time. A central composite design has been used to optimize these 3 parameters and to assess the robustness of the extraction method. The optimal conditions for the quantitative extraction of cocaine from leaves were the following 20 MPa, 80 °C, 1 mL min , 10 min extraction time, with a particle size distribution between 90 and 150 pm. 

Local anaesthetics (LAs) were developed starting from observations on the naturally occurring alkaloid cocaine which occurs in shruh Erythoxylon coca which is found in hoth South America and South-east Asia. South American... 

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