The synthesis of haptens and their use for the development of monoclonal antibodies for treating methamphetamine abuse.
In addition to addiction, the repeated use of (+)-methamphetamine [(+)-METH], (+)-amphetamine [(+)-AMP], or (+/-)-3,4-methylenedioxymethamphetamine ((+/-)-MDMA, commonly called ecstasy) can lead to life-threatening medical problems including cardiovascular injury, severe depression, and psychosis. Currently, there are no specific pharmacotherapies to treat these medical problems. In this study, we report the design and synthesis of two haptens, (S)-(+)-3-(9-carboxynonyloxy)methamphetamine (3a, (+)-METH MO10) and (S)-(+)-3-(5-carboxypentyloxy)methamphetamine (3b, (+)-METH MO6), and their use in generating high affinity (low K(D) value) monoclonal antibodies (mAbs) against (+)-METH, (+)-AMP, and/or (+)-MDMA. On the basis of results from the determination of mAb K(D) values and ligand specificity, the mAbs generated from hapten 3a showed the greatest promise for generating active and passive immunotherapies for treating overdose or addiction from (+)-METH-like stimulants.
Carroll
F Ivy
FI
Center for Organic and Medicinal Chemistry, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, North Carolina 27709, USA. fic@rti.org
Abraham
Philip
P
Gong
Paul K
PK
Pidaparthi
Ramakrishna R
RR
Blough
Bruce E
BE
Che
Yingni
Y
Hampton
Amber
A
Gunnell
Melinda
M
Lay
Jackson O
JO
Peterson
Eric C
EC
Owens
S Michael
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D055808:Drug Discovery; D005260:Female; D006241:Haptens / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D007114:Immunization; D008694:Methamphetamine; D051379:Mice; D010047:Ovalbumin / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D019966:Substance-Related Disorders / Q000276:immunology*; D013379:Substrate Specificity
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D006241:Haptens; D008694:Methamphetamine; D010047:Ovalbumin