Analytical Psychopharmacology Laboratory

T.B. Cooper, M.A., Director

Staff

The Analytical Psychopharmacology Laboratory conducts biochemical pharmacology studies in all major psychiatric disorders.

The primary focus of the laboratory is on the mode of action of psychotropic drugs and metabolites. This research involves the development of assay procedures for the quantitation of psychotropic drugs and their metabolites in body fluids and tissues. In many cases, labeled compounds (deuterium) act as internal standards enabling isotope dilution procedures to be utilized in mass spectrometer procedures. These validated assays are then used in determining the pharmacokinetics and pharmacodynamics of new and existing drugs. Such studies require a range of sophisticated analytical instrumentation to enable quantitation of these compounds at picogram (10-12 g) concentrations.

The pharmacology of enantiomers of drugs are also being studied, using a variety of novel procedures to isolate, separate, quantitate and determine pharmacological activity of these chiral compounds and their respective metabolites. Other major programs examine the mechanism of ethanol tolerance at the cellular and sub-cellular level; the kinetics and hemodynamics of maternal fetal transport of abused drugs; neuroendocrine response in biological challenge paradigms; evaluation of neurotransmitter and/or metabolite profiles in spinal fluid, plasma and urine in man and tissue studies in animals and toxicological studies of drug and drug metabolite concentration in human brain and hair.

The laboratory is the core laboratory for six federally funded Research Center grants and serves as a collaborating laboratory facility to RO-1 grants within NKI and more than 18 other research centers

Notable Achievements by the Analytical Psychopharmacology Laboratory

• First bioequivalence study between generic chlorpromazine and Thorazine (1974)
• First to use N-P detectors in gas chromatography for the analyses of tricyclic antidepressants (1975)
• First to use electrochemical detectors in liquid chromatography for the analyses of hydroxy metabolites of tricyclic antidepressants (1981)
• First to develop 24 hr. single dose prediction techniques for drug plasma level monitoring for lithium, nortriptyline and desipramine (1972-1982)
• First to show the pharmacokinetics for sustained-released lithium formulations (1978)
• First to elucidate the metabolism of bupropion (Wellbutrin) in humans and rodents (1983)
• First to recognize the stereospecific formation of a major active metabolite of bupropion (1997)
• First to develop highly specific polyclonal antibodies to fluphenazine(Prolixin) and dexamethasone (Decadron) for applications in measuring pg/mL levels in clinical pharmacokinetics (1988-1990)
• First to participate in human and rodent pharmaco-kinetic studies measuring plasma levels of the enantiomers of methylphenidate/ritalinic acid using GC/MS (1997-1998)
• First to demonstrate N-desmethylquetiapine in the plasma of quetiapine treated patients using LC/MS for assay and structural confirmation. Clinical correlates are being explored (2002)
• First to identify the involvement of anandamide a naturally occurring marijuana like substance found in the brain and its receptor cannabinoid (CB1) in alcohol drinking behavior (2003)
• Our most recent findings suggest that a dysfunctional endocannabinoid system could be involved in the pathophysiology of mood disorders in depression and suicide (2004)

The Gas Chromatography Laboratory

For further information, contact Mr. Cooper at