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Peter
Jatlow , MD
Professor of Laboratory Medicine and Psychiatry
Director, Clinical Chemistry Laboratory
CB 407 YNHH
203-688-2446
peter.jatlow@yale.edu
1957,
B.S., Union College
1961, M.D., SUNY Down State Medical Center
Fellowship: Yale School of Medicine
Community
of Science Biosketch
Research
Interests
My research is concerned with the clinical pharmacology of psychotropic
drugs, and in particular with the clinical and neuropharmacology of
cocaine. Recently we have been interested in the interactions between
ethanol and cocaine. Most cocaine abusers concurrently use ethanol,
and report that euphoria is prolonged, and the dysphoria of acute
withdrawal is lessened. When the two are self administered concurrently,
cocaine is transesterified in the presence of ethanol with production
of an active metabolite, cocaethylene. We have shown that this metabolite
is equipotent to cocaine in its ability to block dopamine uptake,
inhibit ligand binding to the dopamine transporter, increase dopamine
concentration in brain microdialysate, and is equipotent to cocaine
as a reinforcer in animals. Moreover, while less potent, cocaethylene
has similar behavioral/psychotropic effects in humans. Interestingly,
cocaethylene is much less potent than cocaine in its binding to the
serotonin and norepinephrine transporters. Since cocaethylene is more
slowly eliminated than cocaine, is more specific as a dopamine uptake
inhibitor and has similar but less potent behavioral effects, we have
become interested in it, as well as other C-2 substituted benzoyloxytropanes,
as possible analog substitution treatments for cocaine abuse. In animal
studies, we have found that following chronic infusion with cocaethylene,
locomotor response to a cocaine challenge was blunted consistent with
development of cross-tolerance.
Another
area of interest has been the interaction between medications used
to treat drug abuse and those used for the management of HIV infection.
Our collaborative studies have demonstrated that pretreatment with
methadone increases plasma AUC for AZT provably due to inhibition
of hepatic glucuronidation, but decreases bioavailability of other
nucleosides RTI's. We are currently investigating interactions of
methadone with other antiretrovirals including protease inhibitors,
which are also CYP-450 inhibitors, and non-nucleoside RTI's which
tend to be CYP-450 inducers.
More
recently, as director of a core pharmacology laboratory in conjunction
with a tobacco research center, I have become interested in the
clinical pharmacology of nicotine dependence. We are studying plasma
cotinine concentrations as markers of response and partial response
in smoking cessation studies, as well as the effect of alcohol use
on the correlation of cotinine levels with smoking history. In conjunction
with a pharmacotherapy study I am investigating whether plasma concentrations
of beta-naltrexol (naltrexone metabolite) predict response and/or
toxicity.
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Baker J, Jatlow P, Pade P, Ramakrishnan V, McCance-Katz EF. Acute Cocaine Responses Following Cocaethylene Infusion. J Drug and Alc Abuse, in press
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Baker JR, Jatlow P, and McCance-Katz EF. Disulfiram Effects on Responses to Intravenous Cocaine Administration. Drug and Alcohol Dependence, in press
Toll BA, O’Malley S, Katulak NA,, Wu R, Dubin JA, Latimer A, Meandzija B, George, Jatlow P, Cooney JL, Salovey P. Comparing Gain- and Loss-Framed Messages for Smoking Cessation with Sustained-Release Bupropion: A Randomized Controlled Trial. Psychology of Addictive Behaviors, in press
Toll, BA, McKee, S. A., Martin, DJ., Jatlow, P, O'Malley, S S. Factor structure and validity of the Medication Adherence Questionnaire (MAQ) with cigarette smokers trying to quit. Nicotine & Tobacco Research. In Press
Weinberger SH, Sacco KA, Creeden CL,Vessicchio JC, Jatlow PI, George TP. Effects of acute abstinence, reinstatement, and mecamylamine on biochemical and behavioral measures of cigarettesmoking in schizophrenia. Schizophrenia Res, 91: 217–225, 2007
McCance-Katz EF,1 Moody DM, Smith P, Morse GD,3 Friedland, G Pade P,1 Baker JR, Alvanzo A, Jatlow P, and Rainey PM. Interactions Between Buprenorphine and Antiretrovirals II: Protease Inhibitors, Nelfinavir, Lopinavir/Ritonavir, or Ritonavir. Clinical Infectious Diseases, 43(Supl 4):S235-246, 2006
McCance-Katz EF,1 Moody DM, Morse GD, Friedland, G, Pade P, Baker JR, Alvanzo A, Smith P,3 Ogundele A, Jatlow P and. Rainey PM. Interactions Between Buprenorphine and Antiretrovirals I: Non-Nucleoside Reverse Transcriptase Inhibitors Efavirenz and Delavirdine. Clinical Infectious Diseases, 43(Supl 4):S224-234, 2006
Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, Dubin J, Estock K, Brenner E, Baldwin RM, Tamagnan GD, Seibyl JP, Jatlow PI, Piciotto M, London ED, O’Malley SS and van Dyck C. Human Tobacco Smokers in Early Abstinence Have Higher Levels of beta2 Nicotinic Acetylcholine Receptors than Nonsmokers. J Neuroscience, 26:8707-8714 2006
O'Malley, SS, Cooney JL, Krisna-Sarin S, Dubin JA,McKee SA,Cooney NL, Blakeslee A, Meandzija B, Romano-Dahlgard D, Wu R, Makuch R, Jatlow P. A controlled trial of naltrexone augmentation of nicotine replacaement therapy for smoking cessation. Arch Int Med, 166:667-674, 2006.
Staley JK, Gottschalk C, Petrakis IL, Gueorguieva R, O’Malley SS, Baldwin R, Jatlow P, Verhoeff NP, Perry E, Weinzimmer D, Frohlich E, Ruff E, van Dyck CH, Seibyl JP, Innis RB, Krystal JH. Cortical y-Aminobutyric Acid type A-Benzodiazepine Receptors in Recovery From Alcohol Dependence: : Relationship to features of alcohol dependence and cigarette smoking. Arch Gen Psychiatry, 62: 877-888, 2005
McCance-Katz EF, Rainey PM, Smith P, Morse GD, Friedland G, Boyaarsky B, Gourevitch M, Jatlow P, Drug Interactions between opioids and antiretroviral medications:Interaction between Methadone, LAAM, and Delavridine. Am J Addict 15:23-34, 2006.
Sughondhabirom A, Jain D, Gueorguieva R, Coric V, Berman R, Lynch W, Self D, Jatlow P, Malison R. A Paradigm to Investigate the Self-Regulation of Cocaine Administration in Humans. Psychopharmacology 180:436-446, 2005.
Kosten TA, Sanchez H, Jatlow PI, Kehoe P. Neonatal Isolation Alters the Estrous Cycle Interactions on the Acute Behavioral Effects of Cocaine. Psychoneuroendocrinology 30:753-761, 2005
Epperson CN, O’Malley S, Czarkowski KA, Gueorguieva R, Jatlow P, Sanacora G, Rothman DL, Krystal JH, Mason GF. Sex, GABA, and Nicotine: The Impact of Smoking on Cortical GABA Levels Across the Menstrual Cycle as Measured with Proton Magnetic Resonance Spectroscopy. Biol Psychiatry, 57:44-48, 2005
Sacco KA, Termine A, Seyal AA, Dudas MM, Vessicchio JC, Krishnan-Sarin S, Jatlow P, Wexler BE, George TP. Effects of Cigarette Smoking on Spatial Working Memory and Attentional Deficits in Schizophrenia: Involvement of Nicotinic Receptor Mechanisms. Archives of General Psychiatry 62:649-659, 2005
McCance-Katz EF, Hart CL, Boyarsky BK, Kosten TR, Jatlow P: Gender Effects Following Repeated Administration of Cocaine and Alcohol. Substance Use and Misuse 40:511-528, 2005.
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Jatlow
P, Elsworth JD, Bradberry CW, Winger G, Taylor JR, Russell R and
Roth R. Cocaethylene: A Neuropharmacologically Active Metabolite
Associated with Concurrent Cocaine-ethanol Ingestion. Life Sci
48:1787-1794, 1991.
McCance-Katz
EF, Price LH, McDougle CJ, Kosten TR, Black JE and Jatlow PI.
Concurrent Cocaine-ethanol Ingestion in Humans: Pharmacology,
Physiology, Behavior, and the Role of Cocaethylene. Psychopharmacology
111:39-46, 1993. McCance
Katz EF, Price LH, Kosten TR, Jatlow PI. Cocaethylene: Pharmacology,
physiology and behavioral effects in humans. J Pharmacol Exp Ther
274:215-223, 1995. Bradberry
CW, Lee JW, Jatlow P. Rapid induction of behavioral and neurochemical
tolerance to cocaethylene, a model compound for agonist therapy
of cocaine dependence, Psychopharmacology, 146: 87-92, 1999.
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