Position
Assistant Professor, Department of Pharmacology and Toxicology, College of Medicine
Contact
Email: lbrents@uams.edu
Research Experience
The objective of my laboratory is to develop treatment strategies for opioid use disorder that can be administered to pregnant women without negatively affecting fetuses. Current pharmacological treatments for opioid use disorder during pregnancy include the opioids methadone and buprenorphine, to which the fetus can become physically dependent. This physical dependence leads to neonatal abstinence syndrome (NAS) during the first days and weeks of life. Neonatal abstinence syndrome is a potentially life-threatening withdrawal syndrome that is characterized by inconsolable high-pitched crying, tremor, vomiting, diarrhea, sleep disturbances, and hypersensitivity to stimuli that are normally well tolerated by newborns. Additionally, the life-long effects of in utero opioid exposure or experiencing neonatal abstinence syndrome are poorly understood. Although methadone and buprenorphine often cause neonatal abstinence syndrome, maternal and neonatal outcomes following treatment with the medications are substantially improved relative to no treatment; thus methadone and buprenorphine represent the current best treatments for opioid use disorder during pregnancy.
Buprenorphine treatment is associated with less severe neonatal abstinence syndrome than methadone; therefore, my laboratory is focused on understanding the factors that drive buprenorphine-associated neonatal abstinence syndrome so that we can develop strategies to combat it. Our active projects are examining the contributions of an active metabolite of buprenorphine, called norbuprenorphine, to neonatal abstinence syndrome. Evidence suggests that this metabolite is not important for maternal treatment but is associated with neonatal abstinence syndrome. We envision that reducing fetal exposure to norbuprenorphine during maternal buprenorphine treatment will improve neonatal and life-long outcomes for the offspring. Potential methods to accomplish this goal that we are investigating include shunting buprenorphine metabolism from norbuprenorphine to minor, inactive metabolites, and increasing placental transport of norbuprenorphine from fetal to maternal circulation by p-glycoprotein.
Recent Publications
Tobacyk J, Parks BJ, Salazar P, Coward LU, Berquist MD, Gorman GS, Brents LK.
Interaction between buprenorphine and norbuprenorphine in neonatal opioid
withdrawal syndrome. Drug Alcohol Depend. 2023 Aug 1;249:110832. doi:
10.1016/j.drugalcdep.2023.110832. Epub 2023 Jun 21. PMID: 37385117; PMCID:
PMC10573081.
Janganati V, Salazar P, Parks BJ, Gorman GS, Prather PL, Peterson EC, Alund
AW, Moran JH, Crooks PA, Brents LK. Deuterated buprenorphine retains
pharmacodynamic properties of buprenorphine and resists metabolism to the active metabolite norbuprenorphine in rats. Front Pharmacol. 2023 May 9;14:1123261. doi: 10.3389/fphar.2023.1123261. PMID: 37229250; PMCID: PMC10204800.
Tobacyk J, Brents LK. Response to article – alternative interpretation of
“there is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome”. J Matern Fetal Neonatal Med. 2023 Dec;36(1):2183469. doi: 10.1080/14767058.2023.2183469. PMID: 36863717; PMCID: PMC10246566.
Tobacyk J, Parks BJ, Lovelady N, Brents LK. Qualitative content analysis of
public responses to an FDA inquiry on the impact of scheduling changes to
kratom. Int J Drug Policy. 2022 Oct;108:103817. doi: 10.1016/j.drugpo.2022.103817. Epub 2022 Aug 8. PMID: 35952436; PMCID: PMC10243221.
Kulbeth HJ, Fukuda S, Brents LK. Automated quantification of opioid
withdrawal in neonatal rat pups using Ethovision® XT software. Neurotoxicol
Teratol. 2021 Mar-Apr;84:106959. doi: 10.1016/j.ntt.2021.106959. Epub 2021 Jan 30. PMID: 33529734; PMCID: PMC7965335.