NIDA Research Monograph Series #158: Biological Mechanisms and Perinatal Exposure to Abused Drugs

244 Pages·1995·2.4 MB·English

by  Thadani, Pushpa V. (editor)

National Institute on Drug Abuse
RESEARCH
MONOGRAPH SERIES
Biological
Mechanisms and
Perinatal Exposure
to Drugs
158
U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health

Biological Mechanisms and
Perinatal Exposure to Abused
Drugs
Editor:
aphsuP .V ,inadahT.D.hP
NIDA Research Monograph 158
1995
.S.U TNEMTRAPED FO HTLAEH DNA NAMUHSECIVRES
cilbuP htlaeHecivreS
lanoitaN setutitsnI fo htlaeH
lanoitaN etutitsnI no gurDesubA
noisiviD fo cisaBhcraeseR
0065 srehsiFenaL
,ellivkcoR DM75802
ACKNOWLEDGMENT
sih Thpargonom si desab no eht srepap morf a lacinh cweetiverno
lacigoloi Bs“msinahceM dna latanireP erusopxE ot desubA”sgurD
dleh no yaM ,62-52 .4991 ehT weiver gniteem saw derosnops ybeht
lanoitaN etutitsnI no gurD.esubA
COPYRIGHT STATUS
ehT lanoita NetutitsnI no gurD esubA sah deniat bnooissimrep morfeht
thgirypoc sredloh ot ecudorper niatrec ylsuoiver pdehsilbup lairetamsa
deton ni eht .txet rehtruF noitcudorper fo siht dethgirypoc lairetamsi
dettimrep ylno sa trap fo a gnitnirper fo eht er intonietacilbup ro.retpahc
roF yna rehto ,esu eht thgirypoc s’redloh noissimrep si .deriuqerllA
rehto lairetam ni siht emulov tpecxe detouq segassap morfdethgirypoc
secruos si ni eht cilb unpiamod dna yam eb desu rdoecutduoorhpteirw
noissimrep morf eht etutitsnI ro eht .srohtua noitatiC fo eht ecruossi
.detaicerppa
snoini pdOesserpxe ni siht emulov era esoht fo eht srohtua dna odton
ylirass etcceenlfer eht snoinipo ro laiciffo ycilop fo eht lanoiteatNutitsnI
no gurD esubA ro yna rehto trap fo eht .S .tUnemtrapeD fo htlaeHdna
namuH.secivreS
ehT .S. Utnemnrevo Gseod ton esrodne ro rovaf yna cifilcaeipcsremmoc
tcudorp ro .ynapmoc ,edarT ,yrateirporp ro ynapmoc seman gniraeppani
si hntoitacilbu pera desu ylno esuaceb yeht era dere dliasintoncesse nieht
txetnoc fo eht seiduts detroper.niereh
National lnstitute on Drug Abuse
NIH Publication No. 95-4024
Printed 1995
ADIN hcraeseR shpargonoM era dexedni ni eht Index Medicus. yehTera
dyeldeuvl icntnicie leeeghsatre vfooc American Statistics Index,
BioSciences Information Service, Chemical Abstracts, Current Contents,
Psychological Abstracts, dna Psychopharmacology Abstracts.
ii
Contents
ec a.fe r.P . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1
Pushpa V. Thadani
,-seicepS ,-redneG dna detaleR-y csneacnngeerrePffiDni
sc istce inemiha ktndoyncdaa omfcroaam hrePanhiPacoC . . . . . . . . . . .2
Hisayo O. Morishima and Robert A. Whittington
stceffE fo enihproM dna eniacoC no gnihtaer BlortnoCni
l:astlaanmoie nNw AeAiveri n.iM . . . . . . . . , . . . . . . . . . . . . . . . . . .22
George D. Olsen and Laine J. Murphey
ralucsavo isdtrcaeCffE fo eniacoC ni tnafnIdna
st e .legl ii.Pn e.vu J. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .04
Frank M. Scalzo and Lora J. Burge
stceffE fo eniacoC no lateF niarB msilobateMdna
la reotiavtaS hneiB eh tpe elheSdoM . . . . . . . . . . . . . . . . . . . . . . . . . .85
David J. Burchfield
lateF larbereC ralucsaV stceffE fo eniacoC erusopxE . . . . . . . . . . . . .76
Michael D. Schreiber
stceffE fo latanerP enihproM dna eniacoC nolatantsoP
s rsertotii v mda.snhn aeanBritaor rB.ueN . . . . . . . . . . . . . . . . . . . . .. 88
Ilona Vathy
latanerP eniacoC secudorP lacimehcoiB dnalanoitcnuF
s e sgnmn iean nth inosCnityia oS ryrtBneaeSRgo r.P . . . . . . . . . . .. 115
George Battaglia, Theresa M. Cabrera, and Louis D. Van de Kar
ynegotnO fodecudnI-enimatehpmahteM
ytic inxio teohrt ut ealNRedoM . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 149
Charles V. Vorhees and Cunfeng Pu
y nne ognioott ipnfteOop c edi.cnciaocnoiNtn A. . . . . . . . . . . . . . .. 172
Gordon A. Barr
latanireP enipezaidozneB noitaludoM foABAG
A
rotpeceR :noitcnuF ecneulfnI no evitpadA sesnopseR . . . . . . . . . . .202
Carol K. Kellogg
iii

Preface
Pushpa V. Thadani
nO yaM 52 dna ,62 ,4991 eht lanoitaN etutitsnI no gurD esubA dleha
lacinhceT weiveR deltitne lacigoloi Bs“msinahceM dnalatanireP
erusopxE ot desubA ”sgurD ot weiver dna ssucsid eht-fo-etatstra
sgnidnif ni siht tnatropmi ,aera ot yfitnedi sdeen dna erutufhcraeser
,seitinutroppo dna ot etomorp yranilpicsidret.nsinoitacinummoc
lacide msorieBhcrae sdeerssucsid eht tnecer secnavda ni ehttnempoleved
fo evitavonni lamina sledom dna rieht noitazilitu ot rotindoemcudni-gurd
segnahc ni latef dna lat alnaoceingoloi ssymheptsys rednudellortnoc
.snoitidnoc yehT osla dessucsid eht lacigoloib smsinahcemelbisnopser
rof eht tneisnart ro mret-gnol stceffe fo latanirep erusopxe otdesuba
)s(ecnatsb urso eht kcal fo eseht stceffe dna eht ecnaveler foeseht
latnemir espgxneidnif ni tnereffid lamina seiceps otlacinilc
.snoitavresbo/stroper ehT lacigolodohtem dna citamgidarap seussitaht
deen ot eb deredisnoc dna detargetni ni er ultautfnemire pyxdeutssngised
erew osl.adessucsid
A ecnerefn otcro pgenrizirammus eht rojam sgnidnif dnaeht
lacigolodohtem dna latnemirepx eseussi dessucsid ta eht gniteemdna(
hcihw stsil lla ecn e)rsetfnnaopcicitrap saw dehsilbup ni eht hcraM5991
eussi fo ”espanyS“ inadahT( .)5991 sihT hpargonom stsisnoc foeht
srepap detneserp ta eht lacinhceT weiveR.gniteem
AUTHOR
aphsuP .V ,inadahT.D.hP
margorP/tsigolocamrahP reciffO
noisiviD fo cisaBhcraeseR
lanoitaN etutitsnI no gurDesubA
nwalkraP ,gnidliuB mooR91-A01
0065 srehsiFenaL
,ellivkcoR DM75802
REFERENCES
,inadahT .V.P ecnerefnoC :tropeR lacigoloiB smsinahcem dnalatanirep
erusopxe ot desuba .sgurd Synapse 19:228-232, 1995.
1
Species-, Gender-, and
Pregnancy-Related Differences
in the Pharmacokinetics and
Pharmacodynamics of Cocaine
Hisayo O. Morishima and Robert A. Whittington
INTRODUCTION
A taerg rebmun fo seiduts ni eniac ohccraeser evah de’dsnraephxceraeser
cisab egdelwonk fo e hctigolocamra hdpna cigoloi ssythcpeffe foeniacoc
ni snamuh dna .slamina sihT retpahc lliw ssucsid ,-seiceps ,-rednegdna
detale rs-eyccnnearnegfefripd ni eniaco cnoitisopsid dna woheseht
lacigolo isbrotcaf yam yfidom eht stceffe fo .eniacoc ehT stceffe foetuor
dna edom fo n ogiutradrts itnaihmtda yam esi weecknielulfnieht
,scitenik o,csacmirmaahnpydocamrahp dna ylbissop eht yticixotfo
eniacoc lliw osla eb .denimaxe tI si ton eht ’srohtua esoprup ot edivorpa
etelp mwoeciver fo eht stceffe fo ,eniacoc tub rehtar o tetartsulleiht
ecnatropmi fo eseht srotcaf ni detaicossa-enia ceoscrevda .stceffeeroM
cificep snoitamrof nginidrager latanirep eniacoc erusopxe no ehtsutef
dna nrobwen sah neeb deweiver ni reht osretpahc fo sihthcraeser
.hpargonom
COCAINE METABOLISM, PHARMACOKINETICS, AND
PHARMACODYNAMICS
ehT msilobatem fo eniaco csevlovn ilarev etsneref fsiydawhta perugif(.)1
nI ,snam uehniacoc sah n anoi teafniilm-ifllea hmorf 24 ot 28setunim
ttenraB( te .la )1891 dna si dezilobate myldipar yb eerht rojamsyawhtap
htiw eht tnatluser noitamrof fo owt yramirp :setilobate meninogcelyhtem
retse d n.aeninogcelyozn eebhT etilobate meninogce lyhtem retsesi
thguoht ot eb demrof yb citapeh sa llew sa yb am s,aslepsaretesleihw
noitamrof fo eninogcelyozneb srucco yb ,suoenatnocpistamyznenon
sisylor dyylhralucitrap ta lacigoloisyhp Hp erbmA( te .la ;1991 trawetSte
.la ;9791 naV etteD dna hsimoC.)9891
tuobA 1 ot 2 tnecrep fo eniacoc dseirrefsnart ooitbyll aacigolocamrahp
evitca ,etilo b,aetneimacocron yb na noitalyht enmoeidt-cNaerdezylatac
2
FIGURE 1. Metabolic pathways of cocaine.
yb citapeh lamosorci m.semyzne esehT semyzne yalp na tnatropmielor
ni decudni-gur d.yticixot tI si detseggus taht ehtdecudni-eniacoc
yticixot onteaepseh ni slamina yam eb eud ot eniacocro ndnasti
eetniilaocboactreomn-yxo rsdkywha-HN( te .la ;5791 kayaN te .la.)6791
ehT ’sro hetvuiatara pymtoiccixot yduts fo eniacocron dna eniacoc nistar
setacidni taht eht lahtel esod fo eniacocron si .rellams nI,noitidda
evissam larberec dna cita pseehgahrromeh erew ylnommo cdevresboni
slamina taht deid morf eniacoc raomnihsiroM( te ,.la dehsilbupnu.)atad
ataD osla wohs taht namuh amsalp eniac oscnroointartnecndoecrusaem
g ntinrautdi mloochnooccla dna eniacoc esu era 2 semit rehgih nahtesoht
derusaem ni eht ecneserp fo eniacoc enola erraF( te .la .)3991 tA,tneserp
ti si raelcnu rehtehw eseht desa eesrnncionaiictoacrrtonnec neorcaa
tluser fdoetaler- lsoehgoncalhac ni rehti elamosorc ismemyznero
cificepsnon.sesaretse
nI ,snamu hen isaectoiclobate mera detercx etsoml ayleritne ni eniruhtiw
na noit aenfiimli-lfelah fo 2.4 sruoh rof eninogc elyhtem retsedna
1.5 sruoh rof eninogcelyoz neerbbmA( te .la ,4891 ;8891 notlimaH te.la
1977; Inaba et al. 1978; Jeffcoat et al. 1989; Jindal et al. 1978; Smith
1984).
3
l aechiTgoloca mdrnaahp cixot stceffe fo eniacoc yam eb detaitnetopyb
denibmoc lonahte .esu eniacoC ni eht ecneserp fo lohocla esubasi
demrofsnartoib ot neininogcel y)oeznneelby-hltyehatceoc( yba
cificepsnon rev ielsaretselyxo bnroarcsoB( te .la ;1991 reyoBdna
nesreteP ;1991 naeD te .la 991 ;1 htrowslE te .la .)0991 snoitartnecnoCfo
enelyhte anceotcfo deecxe enhotitartnecn ofco eniacoc ni ,doolb,niarb
,revil dna eniru n-raeH( te .la ;1991 woltaJ te .la .)19 9,1revoeroM nieht
neinaerlbyhtea cyoacm eb a hcum ero mevit ceenliemsa ptosdinoganaht
eniacoc woltaJ( .)3991 sgnidniF osla etacidni taht eniacocdna
enelyhteac oeccudni ralim irsotomoh ctynsaplumits stceffe ni ecimztaK(
te .la .)2991 nO eht rehto ,dnah sa nwohs ni erugif ,2 atad nistar
etartsnomed taht enelyhteacoc si erom tnetop naht eniacoc nignicudorp
lartnec suovren metsys )SNC( dna ralucsavoidrsancoitatsefinam
notgnittihW( te .la .)5991 ,eromrehtruF ekilnu ,eniacoc ereht erewon
-redneg rdoetale rs-eyccnnearnegfefripd ni eht devresebnoelyhteacoc
.yticixot
FIGURE 2. Comparison of the mean (±SE) dose of
cocaethylene (CE) and cocaine (COC) necessary to
produce major toxic manifestations in awake male,
nonpregnant female, and pregnant rats. CE or
COC was infused intravenously at a rate of
2 mg/kg/min.
4