Research Assistant Professor
B.S. 1996, Muskingum University
Ph.D. 2001, University of South Carolina School of Medicine
Dr. Smith is a behavioral pharmacologist and a senior scientist in the NIH-sponsored Anticonvulsant Drug Development (ADD) Program, where she is responsible for the management and new model development for the analgesia core of the program. In hopes of better understanding the comorbidities of epilepsy and their underlying mechanisms, Dr. Smith has incorporated a battery of non-epilepsy, preclinical behavioral models that have been proven successful clinically by identifying molecules with antidepressant, analgesic or anti-manic activity. Her research quantitatively evaluates the therapeutic potential of investigational compounds in both acute and chronic models. Dr. Smith's behavioral profiling differentiates an investigational compound's analgesic profile and its activity in various comorbidities of epilepsy and thus complements the anticonvulsant data compiled by the ADD Program. The identification of novel compounds with broad or unique spectrums of therapeutic activity may help to better clarify the etiology of the comorbidities and the most effective targets for their treatment. Additional related research interests include the role of neuropeptides and steroid hormones in epilepsy and its comorbidities and the sex differences associated with some of these neurological conditions.
Rowley NM, Smith MD, White HS. Hippocampal Betaine/GABA Transporter mRNA Expression is not Regulated by Inflammation or Dehydration post-Status Epilepticus. J. of Neurochem. 2011 Apr;117(1):82-90.
Green BR, Smith M, White KL, White HS, Bulaj G. Analgesic Neuropeptide W Suppresses Seizures in the Brain Revealed by Rationale Repositioning and Peptide Engineering. ACS Chem. Neurosci., 2011, 2 (1), pp 51-56.
Smith MD, Lee HK, Smith BJ, Grussendorf J, Xu L, Gillies RJ, White HS, Bulaj G. Anticonvulsant Met-enkephalin analogues containing backbone spacers reveal alternative non-opioid signaling in the brain. ACS Chem Biol. 2009 Aug 21;4 (8):659-71.
Lee HK, Zhang L, Smith MD, White HS, Bulaj G. Glycosylated neurotensin analogues exhibit sub-picomolar anticonvulsant potency in a pharmacoresistant model of epilepsy. ChemMedChem. 2009 Mar 4(3): 400-5.
White HS, Smith MD. Neurotransmitters and Drug Development in Epilepsy. In Advanced Therapy in Epilepsy. Eds. James W. Wheless, L. James Willmore, and Roger A. Brumback. Sheltoon, Connecticut. People's Medical Publishing House. 2009
Bulaj G, Green BR, Lee HK, Robertson, CR, White K, Zhang L, Sochanska M, Flynn SP, Scholl EA, Pruess TH, Smith MD, White HS. Design, synthesis, and characterization of high-affinity, systemically active galanin analogues with potent anticonvulsant activities. J Med Chem. 2008 Dec 25; 51(24): 8038-47.
Smith, M.D., Saunders G.W., Wilcox, K.S., Clausen, R.P., Frolund, B., Krogsgaard-Larsen, P., Larsson, O.M., Schousboe, A., .and White, H.S. Inhibition of the betaine-GABA transporter (mGAT2/BGT-1) modulates spontaneous electrographic bursting in the medial entorhinal cortex (mEC). Epilepsy Res. 2008 Mar; 79(1):6-13. [Epub 2008 Feb 8.]
Smith, M.D., Adams, A.C., Saunders, G.W., White, H.S. and Wilcox K.S. Phenytoin- and Carbamazepine-Resistant Spontaneous Bursting in Rat Entorhinal Cortex Is Blocked by Retigabine In vitro. Epilepsy Res 2007 May; 74(2-3): 97-106. [Epub 2007 Mar 28.]
Smith, MD, Wilcox, KS and White, HS. Discovery of Antiepileptic Drugs. Neurotherapeutics. 4(1): 12-17. Jan 2007. PMID: 17199014
White HS, Smith MD, Wilcox KS. Mechanisms of action of antiepileptic drugs. Int Rev Neurobiol. 2007; 81:85-110. Review.
Lenkowski, PW Batts, T.W., Smith, MD, Ko SH, Jones, PJ, Taylor, CH, McCusker, AK, Davis, GC, Hartmann, HA, White, HS, Brown, ML, and Patel, MK. A pharmacophore derived phenytoin analogue with increased affinity for slow inactivated sodium channels exhibits a desired anticonvulsant profile. Neuropharmacology. 2007 Mar; 52(3): 1044-54. [Epub 2006 Dec 14.]
Jones, PJ, Wang, Y, Smith, MD, Hargus, NJ, Eidam, HS, White, HS, Kapur, J, Brown, ML, and Patel, MK. Hydroxyamide analogues of propofol exhibit state-dependent block of sodium channels in hippocampal neurons: implications for anticonvulsant activity. J. Pharmacologol Exp Ther. 2007 Feb; 320(2): 828-36. [Epub 2006. Nov. 7.]
Eyal, S. Lamb, J.G., Smith-Yockman, M., Yagen, B., Fibach, E., Altschuler, A., White, H.S., and Bialer, M. The antiepileptic and anticancer agent, valproic acid, induces P-glycoprotein in human tumour cell lines and in rat liver. Br. J of Pharmacol. 2006 Oct;149 (3):250-60. [Epub ahead of print, 2006 Aug 7].
White, HS, Smith-Yockman, M., Srivastava, A. and Wilcox, K.S. Therapeutic Assays for the Identification and Characterization of Antiepileptic and Antiepileptogenic Drugs. In Models of Seizures and Epilepsy. Ed. A. Pitkanen, P.A. Schwartzkroin, and S.L. Moshe. pp.539-549. New York: Elsevier Acad. Press. 2006.