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Bupropion therapy during pregnancy: Concentrations of the drug and its major metabolites in umbilical cord plasma and amniotic fluid
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
attitudes about XR-NTX, suggesting it should be a standard course of treatment for criminally involved and opioid addicted populations. Future research should examine ways to expand its use in criminal justice settings. Financial support: Unfunded pilot survey. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.182 Immune dysregulation in drug addiction? Lisa M. Fleischer ∗ , Nina Tamashunas, Gregory M. Miller Pharmaceutical Sciences, Northeastern University, Boston, MA, United States Aims: Trace Amine Associated Receptor 1 (TAAR1) is a direct target of methamphetamine (METH). It is expressed in the brain reward circuitry where it modulates dopamine (DA) transporter function and DA neuron firing rates. It is also expressed in immune cells and signals through cAMP, similar to adenosine A2 receptors which play a critical role in the immune response. Newly-developed TAAR1-specific compounds have recently been investigated in rodents as candidate therapeutics for METH abuse. These studies involving classic behavioral measures of drug response as well as self-administration strongly implicate TAAR1 as a potential therapeutic target. Immune dysregulation is common in METH abusers. Accordingly, our aims are to define whether TAAR1 and adenosine A2 receptors synergistically elevate cAMP through their Gs coupling in immune cells, and to determine whether TAAR1-specific compounds are therapeutically beneficial via immunomodulatory actions through this shared signaling mechanism. Methods: We are investigating the relationship between TAAR1 and the adenosine A2 receptor at the level of receptor colocalization in specific immune cells, cellular signaling through cAMP, and potential TAAR1/A2 receptor dimerization. Results: In addition to its central actions, we show that TAAR1 is upregulated in peripheral blood mononuclear cells (PBMC) and B cells following immune activation, robustly expressed in immortalized T cell lines, and signals through cAMP in response to METH. Conclusions: TAAR1 and A2 may signal similarly and/or synergistically to regulate immune cell function. A2 signaling through cAMP is immunomodulatory, whereas the immunological consequences of TAAR1 signaling remain unknown. METH has profound effects on the immune system in abusers. Accordingly, deciphering the role of TAAR1 in METH action and immune regulation may lead to the development of novel addiction therapeutics that combat central addictive mechanisms as well as immunological aberrations that occur in drug abuse. Financial support: GMM: Lab start-up funds; LMF: Teaching Assistantship. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.183
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Bupropion therapy during pregnancy: Concentrations of the drug and its major metabolites in umbilical cord plasma and amniotic fluid Valentina M. Fokina 1,∗ , Holly West 1 , Cheryl Oncken 2 , Shannon Clark 1 , Mahmoud S. Ahmed 1 , Gary Hankins 1 , Tatiana Nanovskaya 1 1
OB/GYN Maternal Fetal Medicine, University of Texas Medical Branch, Galveston, TX, United States 2 University of Connecticut Health Center, Farmington, CT, United States Aims: Bupropion (BUP) is used for treatment of the pregnant patients with depressive disorders. Use of BUP as an aid for smoking cessation for pregnant patients is currently under evaluation. The major and pharmacologically active metabolites of bupropion are hydroxybupropion (OHBUP) and threohydrobupropion (TB). The aim of this study is to investigate the in vivo steady state transplacental transfer of BUP and its major metabolites and determine the concentrations of BUP, OHBUP and TB in the amniotic fluid. Methods: Twenty-three pregnant patients under treatment with BUP participated in this study. At delivery the following samples were collected: maternal blood (n = 23), umbilical cord venous (n = 23) and arterial blood (n = 16), and amniotic fluid (n = 9). Individual placental passage for each of BUP, TB and OHBUP was calculated as the concentration ratio of umbilical cord venous plasma to maternal plasma. Results: The concentrations of OHBUP and TB in umbilical cord venous and arterial plasma were lower than their corresponding concentrations in maternal plasma. The mean cordto-maternal ratios were: BUP, 1.11 ± 1.37; OHBUP, 0.22 ± 0.09; and TB, 0.6 ± 0.11. The median concentrations in umbilical cord venous plasma were: BUP, 6.1 ng/ml; OHBUP, 104.2 ng/ml, and TB, 62.9 ng/ml. BUP and its metabolites were detectable in the amniotic fluid, but TB concentrations were higher than those of the corresponding umbilical cord venous plasma. Conclusions: BUP and its major pharmacologically active metabolites cross the placenta to the fetal circulation. The higher levels of TB in the amniotic fluid than those in umbilical cord venous plasma could be explained by the activity of fetal enzymes involved in the metabolism of bupropion. Financial support: The study was supported by RO1 DA030998 to GH and TN, and NICHD U10-HD47891 to TN. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.184
attitudes about XR-NTX, suggesting it should be a standard course of treatment for criminally involved and opioid addicted populations. Future research should examine ways to expand its use in criminal justice settings. Financial support: Unfunded pilot survey. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.182 Immune dysregulation in drug addiction? Lisa M. Fleischer ∗ , Nina Tamashunas, Gregory M. Miller Pharmaceutical Sciences, Northeastern University, Boston, MA, United States Aims: Trace Amine Associated Receptor 1 (TAAR1) is a direct target of methamphetamine (METH). It is expressed in the brain reward circuitry where it modulates dopamine (DA) transporter function and DA neuron firing rates. It is also expressed in immune cells and signals through cAMP, similar to adenosine A2 receptors which play a critical role in the immune response. Newly-developed TAAR1-specific compounds have recently been investigated in rodents as candidate therapeutics for METH abuse. These studies involving classic behavioral measures of drug response as well as self-administration strongly implicate TAAR1 as a potential therapeutic target. Immune dysregulation is common in METH abusers. Accordingly, our aims are to define whether TAAR1 and adenosine A2 receptors synergistically elevate cAMP through their Gs coupling in immune cells, and to determine whether TAAR1-specific compounds are therapeutically beneficial via immunomodulatory actions through this shared signaling mechanism. Methods: We are investigating the relationship between TAAR1 and the adenosine A2 receptor at the level of receptor colocalization in specific immune cells, cellular signaling through cAMP, and potential TAAR1/A2 receptor dimerization. Results: In addition to its central actions, we show that TAAR1 is upregulated in peripheral blood mononuclear cells (PBMC) and B cells following immune activation, robustly expressed in immortalized T cell lines, and signals through cAMP in response to METH. Conclusions: TAAR1 and A2 may signal similarly and/or synergistically to regulate immune cell function. A2 signaling through cAMP is immunomodulatory, whereas the immunological consequences of TAAR1 signaling remain unknown. METH has profound effects on the immune system in abusers. Accordingly, deciphering the role of TAAR1 in METH action and immune regulation may lead to the development of novel addiction therapeutics that combat central addictive mechanisms as well as immunological aberrations that occur in drug abuse. Financial support: GMM: Lab start-up funds; LMF: Teaching Assistantship. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.183
e63
Bupropion therapy during pregnancy: Concentrations of the drug and its major metabolites in umbilical cord plasma and amniotic fluid Valentina M. Fokina 1,∗ , Holly West 1 , Cheryl Oncken 2 , Shannon Clark 1 , Mahmoud S. Ahmed 1 , Gary Hankins 1 , Tatiana Nanovskaya 1 1
OB/GYN Maternal Fetal Medicine, University of Texas Medical Branch, Galveston, TX, United States 2 University of Connecticut Health Center, Farmington, CT, United States Aims: Bupropion (BUP) is used for treatment of the pregnant patients with depressive disorders. Use of BUP as an aid for smoking cessation for pregnant patients is currently under evaluation. The major and pharmacologically active metabolites of bupropion are hydroxybupropion (OHBUP) and threohydrobupropion (TB). The aim of this study is to investigate the in vivo steady state transplacental transfer of BUP and its major metabolites and determine the concentrations of BUP, OHBUP and TB in the amniotic fluid. Methods: Twenty-three pregnant patients under treatment with BUP participated in this study. At delivery the following samples were collected: maternal blood (n = 23), umbilical cord venous (n = 23) and arterial blood (n = 16), and amniotic fluid (n = 9). Individual placental passage for each of BUP, TB and OHBUP was calculated as the concentration ratio of umbilical cord venous plasma to maternal plasma. Results: The concentrations of OHBUP and TB in umbilical cord venous and arterial plasma were lower than their corresponding concentrations in maternal plasma. The mean cordto-maternal ratios were: BUP, 1.11 ± 1.37; OHBUP, 0.22 ± 0.09; and TB, 0.6 ± 0.11. The median concentrations in umbilical cord venous plasma were: BUP, 6.1 ng/ml; OHBUP, 104.2 ng/ml, and TB, 62.9 ng/ml. BUP and its metabolites were detectable in the amniotic fluid, but TB concentrations were higher than those of the corresponding umbilical cord venous plasma. Conclusions: BUP and its major pharmacologically active metabolites cross the placenta to the fetal circulation. The higher levels of TB in the amniotic fluid than those in umbilical cord venous plasma could be explained by the activity of fetal enzymes involved in the metabolism of bupropion. Financial support: The study was supported by RO1 DA030998 to GH and TN, and NICHD U10-HD47891 to TN. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.184