DRUGS 7
1-2nd Coca leaf infusions
Coca herbal infusion (also referred to as coca tea) is used in coca-leaf producing countries much as
any herbal medicinal infusion would elsewhere in the world. The free and legal commercialization of
dried coca leaves under the form of filtration bags to be used as “coca tea” has been actively promoted
by the governments of Peru and Bolivia for many years as a drink having medicinal powers.
Visitors to the city of Cuzco in Peru, and La Paz in Bolivia are greeted with the offering of coca leaf
infusions (prepared in teapots with whole coca leaves) purportedly to help the newly arrived traveler
overcome the malaise of high altitude sickness. The effects of drinking coca tea are a mild stimulation
and mood lift. It does not produce any significant numbing of the mouth nor does it give a rush like snorting
cocaine. In order to prevent the demonization of this product, its promoters publicize the unproven concept
that much of the effect of the ingestion of coca leaf infusion would come from the secondary alkaloids, as
being not only quantitatively different from pure cocaine but also qualitatively different.
It has been promoted as an adjuvant for the treatment of cocaine dependence. In one controversial
study, coca leaf infusion was used—in addition to counseling—to treat 23 addicted coca-paste smokers in
Lima, Peru. Relapses fell from an average of four times per month before treatment with coca tea to one
during the treatment. The duration of abstinence increased from an average of 32 days prior to treatment to
217 days during treatment. These results suggest that the administration of coca leaf infusion plus counseling
would be an effective method for preventing relapse during treatment for cocaine addiction. Importantly,
these results also suggest strongly that the primary pharmacologically active metabolite in coca leaf infusions
is actually cocaine and not the secondary alkaloids.
The cocaine metabolite benzoylecgonine can be detected in the urine of people a few hours after drinking
one cup of coca leaf infusion.
1-2ne Biosynthesis
The first synthesis and elucidation of the cocaine molecule was by Richard Willstätter in 1898. illstätter’s synthesis
derived cocaine from tropinone. Since then, Robert Robinson and Edward Leete have made significant
contributions to the mechanism of the synthesis. (-NO3)
The additional carbon atoms required for the synthesis of cocaine are derived from acetyl-CoA, by addition of
two acetyl-CoA units to the N-methyl-1-pyrrolinium cation. The first addition is a Mannich-like reaction with the
enolate anion from acetyl-CoA acting as a nucleophile towards the pyrrolinium cation. The second addition occurs
through a Claisen condensation. This produces a racemic mixture of the 2-substituted pyrrolidine, with the retention
of the thioester from the Claisen condensation. In formation of tropinone from racemic ethyl 4(Nmethyl-2-pyrrolidinyl)
-3-oxobutanoate there is no preference for either stereoisomer. In the biosynthesis of cocaine, however, only the
(S)-enantiomer can cyclize to form the tropane ring system of cocaine. The stereoselectivity of this reaction was
further investigated through study of prochiral methylene hydrogen discrimination. This is due to the extra chiral
center at C-2. This process occurs through an oxidation, which regenerates the pyrrolinium cation and formation
of an enolate anion, and an intramolecular Mannich reaction. The tropane ring system undergoes hydrolysis,
SAM-dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety
required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid. Benzoyl-
CoA then combines the two units to form cocaine.
1-2nf N-methyl-pyrrolinium cation
The biosynthesis begins with L-Glutamine, which is derived to L-ornithine in plants. The major contribution of
L-ornithine and L-arginine as a precursor to the tropane ring was confirmed by Edward Leete. Ornithine then undergoes
a pyridoxal phosphate-dependent decarboxylation to form putrescine. In animals, however, the urea cycle derives
putrescine from ornithine. L-ornithine is converted to L-arginine, which is then decarboxylated via PLP to form agmatine.
Hydrolysis of the imine derives N-carbamoylputrescine followed with hydrolysis of the urea to form putrescine.
The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM-dependent
N-methylation of putrescine gives the N-methylputrescine product, which then undergoes oxidative deamination by the
action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the
N-methyl-1-pyrrolinium cation.
1-2ng Robert Robinson’s acetonedicarboxylate
The biosynthesis of the tropane alkaloid, however, is still uncertain. Hemscheidt proposes that Robinson’s
acetonedicarboxylate emerges as a potential intermediate for this reaction. Condensation of N-methylpyrrolinium
and acetonedicarboxylate would generate the oxobutyrate. Decarboxylation leads to tropane alkaloid formation.
1-2nh Reduction of tropinone
The reduction of tropinone is mediated by NADPH-dependent reductase enzymes, which have been characterized
in multiple plant species. These plant species all contain two types of the reductase enzymes, tropinone reductase I
and tropinone reductase II. TRI produces tropine and TRII produces pseudotropine. Due to differing kinetic and pH/activity
characteristics of the enzymes and by the 25-fold higher activity of TRI over TRII, the majority of the tropinone reduction is
from TRI to form tropine.
1-2ni Detection in body fluids
Cocaine and its major metabolites may be quantified in blood, plasma, or urine to monitor for abuse, confirm a diagnosis
of poisoning, or assist in the forensic investigation of a traffic or other criminal violation or a sudden death.
Most commercial cocaine immunoassay screening tests cross-react appreciably with the major cocaine metabolites,
but chromatographic techniques can easily distinguish and separately measure each of these substances.
When interpreting the results of a test, it is important to consider the cocaine usage history of the individual, since a
chronic user can develop tolerance to doses that would incapacitate a cocaine-naive individual, and the chronic user
often has high baseline values of the metabolites in his system. Cautious interpretation of testing results may allow a
distinction between passive or active usage, and between smoking versus other routes of administration. In 2011,
researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence
of cocaine and other drugs in urine. Similar claims have been made in web forums on that topic.
According to a 2007 United Nations report, Spain is the country with the highest rate of cocaine usage (3.0% of adults
in the previous year). Other countries where the usage rate meets or exceeds 1.5% are the United States (2.8%),
England and Wales (2.4%), Canada (2.3%), Italy (2.1%), Bolivia (1.9%), Chile (1.8%), and Scotland (1.5%).
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