Biological activity of the alkaloids of Erythroxylum coca and Erythroxylum novogranatense

14 Pages·2002·1.05 MB·English

lanruoJ of ,~olocumrahponhtE 10 (1984) 261-274 261
reiveslE cifitneicS srehsilbuP dnalerI Ltd.
Review Paper
BIOLOGICAL ACTIVITY OF THE ALKALOIDS OF ERYTHROXYLUM
COCA AND ER YTHROXYLUM NOVOG~NATEN~E
M. ,aK?VON .A.C aKNIMELAS dna .I bNAHK
tnemtrape)Ia of Organic yrtsimehC of larutaN Products, Organic lacimehC Laboratory,
etatS ~t~~eu~~~ of ,thcertU thcertU ehT( )~~rehteN dna noisivXIb of latnem realty,
dlroW htlaeH ,noitazinagrO Geneva (Switzerland)
detpeccA( yraurbeF ,dn22 1984)
Summary
ehT detavitluc
Erythroxylum varieties E. coca var. coca, E. coca var.
dna E.
~~adu, E. no~gra~tense var. ~vo~a~te~~ no~~nate~e var.
niatnoc 18 ,sdiolakla deifitnedi os far, gnignoleb ot eht ,senaport
truxiffense
senidilorryp dna htiw eniacoc as eht niam .diolakla ehT lacigoloib
ytivitca fo eht gniwollof sdiolakla sah neeb detroper ni eht :erutaretil
,eniacoc ,eniacoclyomannic ,eninogcelyozneb ,eninogcelyhtem -oduesp
,eniport ,enipo~lyozneb ,eniacocaport -yc dna ~-t~x~~e, ,enirgyh -ocsuc
enirgyh dna .enitocin ehT lacigoloib ytivitca fo eniacoc dna enitocin si ton
deweiver ,ereh esuaceb ti si dessucsid erehwesle ni eht .erutaretil yldraH -yna
gniht si nwonk tuoba eht lacigoloib ytivitca fo eht rehto sdiolakla tneserp ni
eht ruof seiteirav .denoitnem ehT sisehtnysoib fo eht acoc sdiolakla sah neeb
.deniltuo
--
Introduction
Historical background
acoC sevael evah neeb dewehc yb eht htuoS naciremA snaidnI ot tneverp
regnuh esaercni ecnarudne rof revo 5000 .sraey nevE yadot ti si desu
and to
as a tnalumits dna enicidem ni ynam strap fo eht sednA dna ni eht nozamA
nisab ,nitraM( ;0791 ,namwolP 1979a). ehT acoc burhs si eno fo eht tsedlo
detavitluc stnalp fo htuoS .aciremA sA yltnecer dezingocer ,namwolP(
1982), eht detavitluc acoc stnalp gnoleb ot owt tcnitsid seiceps fo eht suneg
ylimaf( :)eae~alyxor~~E .maL
E~throxyfum Eryth~xyium coca and E.
)sirroM( .noreiH nihtiW eht suneg eseht owt
novogmnatense E~throxyfum,
06.40$/48/1478-8730 0 1984 reiveslE cifitneicS srehsilbuP dnalerI Ltd.
dehsilbuP dna detnirP ni dnalerI
262
cultivated species are more closely related to each other than to any of
more than 200 wild species.
Each of the cultivated species of coca includes two varieties (Bohm et al.,
1982; Plowman and Rivier, 1983). E. coca Lam. var. coca, “Bolivian” or
“Huanuco coca”, is the best known variety and is still widely cultivated in
the Andean region for legal and illegal production of cocaine. E. coca var.
ipadu Plowman, “Amazonian coca”, is a little known variety of E. coca
which is sparingly cultivated by a number of Indian tribes in the western
part of the Amazon basin (Plowman, 197913). E. nouogrunatense (Morris)
Hieron. var. nouogranatense, “Colombian coca”, is now found as a planta-
tion crop only in Colombia, where it is cultivated by a few isolated Indian
tribes. It is, however, widely grown throughout tropical countries as an
ornamental plant (Plowman and Rivier, 1983). E. nouogrunutense var.
truxillense (Rusby) Plowman, “Trujillo coca”, is mostly confined to the
desert areas of northern Peru (Plowman, 197913). It is cultivated for coca
chewing as well as for the flavouring of beverages (Plowman, 1982; Merory,
1968). Based on morphological, chemical, ecological and reproductive
studies, E. coca var. coca is considered the most primitive among the
cultivated cocas and appears to be ancestral to the other three cultivated
varieties; these three varieties are known only as cultivated plants and
possibly arose through human selection in cultivation (Bohm et al., 1982).
The principal alkaloid found in the cultivated varieties of coca is cocaine.
Today the use of cocaine in medicine as a topical anesthetic is limited,
because of its ability to induce dependence.
In western society cocaine hydrochloride is used illicitly by sniffing it.
Since the early 197Os, another form of cocaine abuse is smoking this
alkaloid in the form of cocaine paste or cocaine base, mixed with tobacco
or marihuana (Siegel, 1979; Paly et al., 1982). The grey-white cocaine
paste is a crude extract of coca leaves, and is reported to contain 40-- 70%
cocaine base along with cocaine salts, other coca alkaloids and traces of
residual organic solvents (Paly et al., 1982). Recently an investigation of
cocaine base smoking has appeared in the literature (Perez-Reyes et al.,
1982).
As the abuse of coca leaf and cocaine creates problems for the health
of individuals, they have been scheduled in the Single Convention on
Narcotic Drugs, 1961, United Nations (see Appendix).
The objective of this review
Coca leaves were originally, and in South America still are, usually chewed.
The use of cocaine, the main alkaloid from the cultivated coca plants -
sniffed in more or less pure form - is strongly increasing and for some years
a new development in this area has been the smoking of coca paste (mixed
with tobacco or marihuana). The acute and chronic effects of coca paste
smoking are more extreme than those of cocaine sniffing, e.g. severe person-
ytila noitargetnisid gnidulcni dionarap dna citohcysp roivaheb as llew as
,snoitanicullah laicos noitalosi dna aixerona yam rucco ylaP( te al., 1980).
roF eht rettal erom citamard stceffe tnalp stneutitsnoc rehto naht eht
diolakla eniacoc thgim eb elbisnopser dna eht ecneuqesnoc fo gnikoms eht
acoc etsap tsum eb nekat otni noitaredisnoc as .llew
ehT evitcejbo fo siht repap si ot weiver eht elbaliava egdelwonk -nrecnoc
gni eht lacigoloib ytivitca fo eht sdiolakla tneserp ni mulyxorhtyrE coca dna
E. nouogranaterzse. ehT lacigoloib ytivitca fo eniacoc lliw ton eb deweiver
ereh ecnis eht ygolocamrahp fo eniacoc sah neeb yletauqeda derevoc yb
srehto ,eluM( ;6791 doownillE dna ;yebliK 1977). enitociN hcihw si
detroper ot rucco ni detavitluc acoc lliw ton eb dessucsid ereh ecnis ti si a
yrev llew nwonk tneutitsnoc fo eht occabot tnalp dna eht ygolocamrahp fo
enitocin sah neeb dezirammus yb srehto ,llayR( 1974).
ehT lacigoloib ytivitca fo eht sdiolakla-non deifitnedi os far morf eht
detavitluc acoc stnalp lliw ton eb deweiver ,ereh esuaceb elttil si tey .nwonk
,revewoH eseht stnenopmoc yam yalp na tnatropmi elor ni acoc etsap
.gnikoms
Literature sources
nI gniraperp eht tneserp troper eht gniwollof erutaretil secruos evah neeb
dehcraes yb( )retupmoc :
:seirtnE Erythroxylum; Erythroxylon; ;acoc rof
lacimehC stcartsbA 1967 - emuloV 98, eussI 24, 1983
:seirtnE eht laudividni sdiolakla as detsil ni elbaT 1, rof
lacimehC stcartsbA 1967 - emuloV 98, eussI 24,1983
atprecxE acideM 1975 - 1983, eussI 5 *
lanoitanretnI ~citueca~hP stcartsbA 1970 - enuJ 1983
yrtsimehC
ehT yrtsimehc fo eht detavitluc acoc stnalp sah neeb deweiver yb tioB
(1961) pu ot 1960 dna yb reuangeH (1966) pu ot 1965. ecniS neht ylno
enirgyhocsucordyhid sah neeb deifitnedi as a wen acoc diolakla gunaH( te
al., 1981). nnameiN ni 1860 detalosi eniacoc as eht tsif diolakla morf eht
sevael fo detavitluc acoc relhiiW( dna ,nnameiN 1860). rehtO sdioIakla fo
eht detavitluc acoc stnalp as detsil ni elbaT 1 gnoleb ot eht ,enaport -ilorryp
enid dna enidiryp .sdiolakla
ehT suneg Erythroxylum si eht ylno larutan ecruos fo eht diolakla ,eniacoc
nwonk os far. eniacoC sah neeb deifitnedi ot etad ni 18 dliw Erythroxylum
,seiceps gnidulcni lareves morf eht dlO dlroW ees( elbaT 1). ehT dliw seiceps
dewohs ylno ecart seititnauq fo ,eniacoc tpecxe owt seiceps morf ,aleuzeneV
E. recovers rebuH dna E. steye~arkii ,namwolP hcihw deniatnoc eniacoc
slevel elbarapmoc ot esoht dnuof ni eht ruof detavitluc seiteirav fo acoc
namwolP( dna ,reiviR 1983).
264
ELBAT 1
SDIOLAKLA IDENTIFIED IN THE RUOF SEITEIRAV FO DETAVITLUC ACOC
rehtO secruos ni Erythroxylum seiceps
-
Tropane alkaloids
eniacoC relhoW( dna ,nnameiN 1860) .E acuminatum ).mA( .plaW tdetsmloH( te ,.la
1977)
.E areolatum .L namwolP( dna ,reiviR 1983)
.E campestre .tS .liH nailinyA( te ,.la 1974)
.E deciduum .tS .liH nailinyA( te ,.la 1974)
.E fimbriatum .ryeP namwolP( dna ,reiviR 1983)
.E glaucum .E.O zluhcS namwolP( dna ,reiviR
1983)
.E gracilipes .ryeP namwolP( dna ,reiviR 1983)
.E .ffa impressum .E.O zluhcS namwolP( dna
,reiviR 1983)
.E incrassatum .E.O zluhcS namwolP( dna
,reiviR 1983)
.E lucidum .K.B.H namwolP( dna ,reiviR 1983)
.E macrocnemium .traM namwolP( dna reiviR
1983)
.E panamense .zcruT nailinyA( te ,.la 1974)
.E pegeterianum .tS .liH nailinyA( te ,.la 1974)
.E pulchrum .tS .liH nailinyA( te ,.la 1974)
.E recurrens rebuH namwolP( dna ,reiviR 1983)
.E rotundifolium nanuL namwolP( dna ,reiviR
1983)
.E shatona edirbcaM namwolP( dna ,reiviR 1983)
.E steyewnarkii namwolP namwolP( dna ,reiviR
1983)
eniacoclyomanniC ,lesaiG( 1889) ,E monogynum .bxoR arpohC( dna ,hsohG
1938)
eniacoclyomanniC-sic ,erooM( 1973) .E pukhrum .tS .liH namwolP( dna ,reiviR 1983)
.E recurrens rebuH namwolP( dna ,reiviR 1983)
.E rotundifolium nanuL namwolP( dna ,reiviR
1983)
.E steyermarkii namwolP namwolP( dna ,reiviR
1983)
eniacoclyomanniC.snart ,erooM( .E recurrens rebuH namwolP( dna ,reiviR 1983)
(1973)
.E steyermarkii namwolP namwolP( dna ,reiviR
1983)
eninogcelyozneB ,kcreM( 1885)
eninogcelyhteM ed( ,gnoJ 1939) .E dekindtii ).lgnE( .E.O zluhcS sopmaC( seveN
dna sopmaC ,seveN 1966)
enidinogcelyhteM ttehctaM( dna .E dekindtii ).lgnE( .E.O zluhcS ayhaY-lA( te ,.la
,eniveL 1941) 1979)
eninogcelymrofroN ed( ,gnoJ 1948)
eniportoduesP reuangeH( dna .E dekindtii ).lgnE( .E.O zluhcS sopmaC( seveN
,rehcsnekiF 1960) dna sopmaC ,seveN 1966)
.E macrocarpum .E.O zluhcS ,snavE( 1981)
.E monogynum .bxoR ragA( dna ,snavE 1976)
265
TABLE 1 (co~~jnued)
Other sources in Erytkroxylum species
Tropane alkaloids (continued)
Benzoyltropine (Wolfes and E. eZZjpticum LF Br. (Johns et al., 1970)
Hromatka, 1933)
.E macrocarpum O.E. Schulz (Evans, 1981)
Tropacocaine (Liebermann, 1891) .E dekindtii (Engl.) O.E. Schulz (Campos Neves
and Campos Neves, 1966)
.E macrocarpum O.E. Schulz (Evans, 1981)
Dihydroxy~opane (Wolfes and
Hromatka, 1933)
cr-Truxilline (Liebermann, 1888)
p-Truxilline (Liebermann, 1888)
Pyrrolidine alka~o~s
Hygrine ( Liebermann, 1889) E. au&rate F. Muell. (Klein and Soos, 1929)
Hygroline (Spiith and Kittel, 1943)
Cuscohygrine (Liebermann and
Cybulski, 1896)
Dihydrocuscohygrine (Hanug et al., 1981)
Pyridine alkaloids
Nicotine (Fikenscher, 1958)
Both cocaine and cinnamoylcocaine were identified in all four varieties of
cultivated coca (Plowman and Rivier, 1983). Cinnamoylcocaine was found
in higher concentration in the two varieties of E. ~o~~~te~e naht ni
either variety of E. coca E. coca var. udapi contained less cocaine than E.
coca var. coca. The dried leaves of the most cultivated variety, E. coca var.
coca, contain approx. 0.6% cocaine (Plowman and Rivier, 1983). The
content of cocaine decreases significantly during storage due to hydrolysis
(Ayn~i~ et al., 1974; de Jong, 1948).
The possibility of formation of artifacts during the extraction of alkaloids
from the coca leaves has been mentioned (Rivier, 1981). Using a mild extrac-
tion method and analysis by gas chromatography-mass spectrometry, it was
established that cocaine and cis- and tmns-cinnamoylcocaine were the endo-
genous alkaloids in the coca leaves; none of the other volatile alkaloids
previously reported in the literature could be detected in the material used
(Rivier, 1981). The occurrence of nicotine in the coca leaves, identified only
by thin-layer chromatography and colour reactions with specific reagents
(Fikenscher, 1958), could not be confirmed (Rivier, 1981).
Rcgonine can be easily converted to cocaine by chemical processes. All
other alkaloids from the plant material besides cocaine which yield ecgonine
after hydrolysis, e.g. cinnamoylcocaine, benzoylecgonine, methylecgonine,
662
-ro and ,enillixurt-@ tonnac eb detcelgen as yeht era llits lufesu rof eht -ehtnys
sis fo eniacoc aiv .eninogce
ehT sdiolakla fo seiceps evah neeb delipmoc yb snavE
Erythroxylum
.)1891( ehT ymonoxatomehc fo eht eaecalyxorhtyrE has neeb deweiver yb
reuangeH .)1891(
ehT sisehtnysoib fo enaport sdiolakla has neeb ylevisnetxe detagitsevni ni
suoecanalos plants ,ekiemoR( ;8791 ,eteeL )9791 and ni ,eteeL(
E. coca
.)3891,2891 tI has neeb nwohs that eht enidilorryp gnir fo enaport -igiro
setan morf enihtinro and that eht smota-C 23 and 4 evired morf owt -elom
seluc fo etateca ,ekiemoR( .)8791 ehT emas noitautis has neeb nwohs ot
dloh rof eht enidilorryp sdiolakla enirgyh waGcM( and ,yellooW )9791 and
enirgyhocsuc ,ekiemoR( .)8791 enitociN is devired morf enihtimo and -ocin
cinit dica namssieG( and ,tuorG .)9691 An eniltuo fo eht sisehtnysoib fo eht
sdiolakla deifitnedi ni eht detavitluc acoc plants is detneserp ni .giF 1.
lacigoloiB ytivitca
ehT lacigoloib ytivitca fo eniacoc and enitocin is ton dessucsid ,ereh rof
snosaer denoitnem .reilrae oN tnecer erutaretil was dnuof gninrecnoc eht
ii<“““” -
NH2 NH2
NH,HC NH2 CHjHN NH2
zHC crteCaoteca acid
emrgyh - a - cilyxobroc acid munilorryp-’A-lyhtem-N lonatubommolyhtem-L
noitac
/ \
-3
clmtocin ocld
0
enoniport
C”3
1
~CH2-C*--CH*q NC
I I
OH
CH3 CH3 4
~irgy~csuc eniportoduesp
267
hygrme -IX- corboxylic acid
C”, ,W hC,
N' N N
&r 4 &
COOCH, COOH COOCH,
0-CO-C,H, OH OH
cocaine ecgonine melhylecgonine
CH, CH, H
N’ N’ N’
COOCH, COOH COOH
& 0-CO-;=;-CC,H, & O-CO-&H, Er 0-CHO
CIS- cln”amoylcocal”e benzoylecgonme “orformylecgcmine
,CHx , CH,
N N
COOCH,
COOCH,
\
H
4r 0-CO-;=C-C,H, 27
tram-cinnamoylcocame methylecgonidine
COOR
H5(k$6H5 H5@!$OOR &CO::H,
H COOR H H
oL- truxillme p- truxllline
IJ-~H-CO-CH, ~CH?- CH- CH, FJ--CH~-CH-CH~~
AH 3 COOH % I HA C IH, bH C IHJ
hygrine -a-carboxyhc hygrolm? dihydrocuscohygrine
acid
5H6c_oc_;&
,W ,W
N $/
A
-
HO4’
1
0
0-CO-C,H, OH
tropinone benzoyl tropine lropacocaine dlhydroxytropane
Fig. 1. Alkaloids identified in the cultivated coca plants - an outline of their biosynthesis.
862
biological activity of the tropane alkaloids methylecgonidine, norformyl-
ecgonine, pseudotropine, dihydroxytropane, cY-truxillinea nd p-truxilline, and
the pyrrolidine alkaloids hygrine, hygroline and dihydrocuscohygrine.
Cinnamoylcocaine
3%
A solution of cinnamoylcocaine in diluted hydrochloric acid showed
no mydriatic and anesthetic properties in cats (Chopra and Ghosh, 1938).
Cinnamoylcocaine has no pharmacological activity (Woker, 1953a). At daily
doses of 60 mg/kg c~namoylcoc~e orally, mice exhibited normal immune
responses (Watson et al., 1983). Mice dosed with 60 mg/kg cinnamoylco-
Caine had suppressed plaque forming cell/lo6 spleen cell responses (Watson
et al., 1983). The plaque forming cell/spleen responses were significantly
suppressed in mice treated with cinnamoylcocaine (Watson et al., 1983).
Benzoylecgonine
Benzoylecgonine does not show an appreciable anesthetic action (Carney,
1955). When tested for pharmacological activity in rats, benzoylecgonine was
inactive after systemic administration, but had potent stimulant activity
when administered centrally (Williams et al., 1977). The dopamine uptake
into the synaptosomal fraction of rat striatum is affected by benzoylecgonine;
the dose is biphasi~~response curve with inhibition of dopamine uptake at
concentrations of lo-’ M or lower (Waifs et al., 1977). No observable
pharmacological effects are noted in the rat after doses of 250 mg/kg
benzoylecgonine intravenously (Misra et al., 1975). At the concentration of
1 mg/kg benzoylecgonine (intracistemally), piloerection, running and jump-
ing activity, jerking, rapid breathing and squeaking appeared within 5 min
and these effects lasted for approximately 4 h; with higher-doses (2 mg/kg)
these effects became more violent without ensuing mortality (Misra et al.,
1975). Benzoylecgonine mildly depresses the excitability and contractility of
striated muscle of the frog and the rat (Kubota and Macht, 1919). Also in
doses from 1 to 3 mg, benzoylecgonine produced no effect upon the behavior
of white rats in the circular maze (Macht and Bloom, 1921). Benzoylecgo-
nine showed no motility increase in mice after doses of l-50 mg/kg sub-
cutaneously and lo-50 mg/kg orally, and no ~pa~ent of retention capa-
bility after administration of 0.3-50 mg/kg orally (Nieschulz, 1971). The
activity of mice impaired by chloropromazine was increased after administra-
tion of 0.1-10 mg/kg benzoylecgonine orally (Nieschulz, 1971). Benzoyl-
ecgonine failed to show cocaine-induced liver damage in mice (Thompson
et al., 1979). It is approximately 20 times less toxic than cocaine (Woker,
1953a). In rats, benzoylecgonine failed to inhibit the accumulation of
[3H]norepinephrine and [‘Hldopamine by synaptosomes from the cortex
and striatum, respectively (Komiskey et al., 1977). At a concentration of
10V3 M, benzoyleegonine produced approximately 40% inhibition of vera-
t~dine-st~ulat~ 22Na+u ptake in an assay with rat brain membrane homo-
genate (Matthews and Collins, 1983). At daily doses of 60 mg/kg benzoyl-
ecgonine orally, mice exhibited normal immune responses (Watson et al.,
1983). Mice dosed with 60 mg/kg benzoylecgonine had suppressed plaque
forming cell/lo6 spleen cell responses (Watson et al., 1983). Benzoylecgonine
did not affect the formation and release of [ “Cldopamine in synaptosomal-
mitochondrial preparations from the caudate nucleus of rat brain (Bagchi
and Reilly, 1983). In the presence of reserpine, which inhibited the synthe-
sis and enhanced the release of [“C]dopamine, benzoylecgonine had no
effect on the formation of [“C]dopamine at a concentration of 9.1 X 10T6
M, but at the 36.4 X 10s6 M level it showed small but significant additional
inhibitory effect; the release of [“Cldopamine in the presence of reserpine
was not further enhanced by the addition of benzoylecgonine (Bagchi and
Reilly, 1983).
Me th ylecgonine
Methyl~gon~e shows no ~esthe~c properties (Takman and Camougis,
1970). At concentrations of 5 X 10m3M and higher, it has significant inhibi-
ting effect on dopamine uptake into the synaptosomal fraction of rat
striatum (Williams et al., 1977). At a concentration of 10m4M , methylecgo-
nine produced approximately 30% inhibition of veratridine-stimulated “Na*
uptake in an assay with rat brain membrane homogenate (Matthews and
Collins, 1983). In the rat, no observable pharmacological effects are noted
with me~yl~gonine after high-doses (200 mgfkg intravenously or 10 mg/kg
~trac~ternally) (Misra et al., 1975). Methyl~gon~e failed to show cocaine-
induced liver damage in mice (Thompson et al., 1979). At daily doses of
60 mg/kg methylecgonine orally, mice exhibited normal immune responses
(Watson et al., 1983). Mice dosed with 60 mg/kg methylecgonine did not
have suppressed plaque forming cell/lo6 spleen cell responses (Watson et al.,
1983).
Pseudo trup~ne
Pseudotropine is almost devoid of atropine-like activity; it has only slight
activity on ganglia (Gyermek and Nader, 1957).
Benzoyltropine
Benzoyltropine shows a strong cholinolytic action, but has hardly any
anesthetic effect (Nader and Scheiber, 1972). It has mild mydriatic proper-
ties (Woker, 1953b). Benzoyltropine shows both potency and selectivity as
an antagonist of 5-hydroxytryptamine on the rabbit heart (Fozard et al.,
1979). In rats, benzoyltropine inhibits the [3H]norepinephrine and C3H]-
dopamine uptake in the cortex and striatum, respectively (Komiskey et al.,
1977).
Tropacocaine
,eniacocaporT hguohtla erom tnatirri than ,eniacoc is detroper ot evah
yletamixorppa eht emas citehtsena noitca as eniacoc htiw eno flah fo its
yticixot ,egreoD( ;1791 redaN and ,rebiehcS .)2791 tI is desu yllapicnirp ni
spinal aisehtsena ,egreoD( .)1791 eniacocaporT deliaf ot wohs -eniacoc
decudni revil egamad ni ecim nospmohT( te al., .)9791 nehW deretsinimda
yllaenotirepartni ot decudni-latibrabonehp ,ecim eniacocaport did ton
ecudorp yticixototapeh nameerF( and ,nosibraH .)1891 tI shows hcum less
citylonilohc noitca than ,eniportlyozneb yllaicepse no eht cinoilgnagtsop
srotpecer fo eht eye rodaN( and ,rebiehcS .)2791 nI rats, eniacocaport
stibihni eht [ enirhpeniperon]H3 and [ enimapod]H3 ekatpu ni eht xetroc and
,mutairts ylevitcepser yeksimoK( te al., .)7791 tI shows htob ycnetop and
ytivitceles as an tsinogatna fo enimatpyrtyxordyh5 no eht tibbar traeh
drazoF( te al., .)9791 eniacocaporT has on citairdym seitreporp ,rekoW(
.)b3591
Q- and S-Truxilline
CX- and enillixurT-3( evah on citehtsena noitca ,rekoW( .)a3591 yehT era
gnorts traeh snixot ,nnamrebeiL( .)8881
Hygrine
enirgyH has on citehtsena noitca ,rekoW( .)a3591
Cuscohygrine
enirgyhocsuC was dnuof ot tibihni eht deyaled epyt ytivitisnesrepyh
esnopser ot enezneboroulfortinid-4,2 ni ;ecim ti decudorp %42 noitibihni
at yliad sesod fo 60 gk/gm nostaW( te al., .)3891 eciM desod htiw 60 gk/gm
enirgyhocsuc had desserppus euqalp gnimrof 6ol/llec neelps llec sesnopser
nostaW( te al., .)3891
snoisulcnoC
ehT detavitluc acoc plants edulcni ruof :seiteirav
Ery throxylum coca var.
.rav and
coca, E. coca var. ipadu, E. novogranatense novogranatense E.
.rav nI tsom fo eht detagitsevni dliw
novogranatense truxillense. Erythroxy-
mul seiceps ylno ecart stnuoma fo eniacoc erew .detceted ,revewoH owt
seiceps morf ,aleuzeneV and deniatnoc eniacoc
E. recurrens E. steyermarhii,
slevel elbarapmoc ot esoht dnuof ni eht ruof detavitluc seiteirav fo .acoc
nI tsartnoc ot eht egral tnuoma fo erutaretil gninrecnoc eht ygolocamrahp
fo ,eniacoc ereht is ylevitaler elttil nwonk tuoba eht lacigoloib ytivitca fo