Neuroscience, Pharmacology, Aging.
Our laboratory studies opioids and their role and mechanisms of action in alleviating pain and inducing side effects, particularly drug abuse. Our current focus is on development of novel, safer analgesics based on modifications of naturally occurring opioids discovered in our laboratory (endomorphins). One compound is in clinical trials and a second generation of analogs has been shown in animal models to provide analgesia equal to or greater than morphine with substantial reduction or absence of several major side effects. These include reduced risk of abuse, respiratory depression, tolerance, pro-inflammatory responses, and side effects of particular importance for older adults, including motor and cognitive impairment.
Zadina, J.E., M.R. Nilges, J. Morgenweck, X. Zhang, L. Hackler, M.B. Fasold. Endomorphin Analog Analgesics with Reduced Abuse Liability, Respiratory Depression, Motor Impairment, Tolerance, and Glial Activation Relative to Morphine. Neuropharmacology 105:215-227, 2016. doi:10.1016/j.neuropharm.2015.12.024[Epub ahead of print]
Chakrabarti, S.N-J Liu, J.E. Zadina, T. Sharma., and A.R. Gintzler. Pleiotropic opioid regulation of spinal endomorphin-2 release and its adaptations to opioid withdrawal are sexually dimorphic. J. Pharmacol. Exper.Ther. 340(1): 58-63, 2012.
Morgenweck, J., R.R. Donahue, A.C. New, J.E. Zadina, B.K. Taylor. PPARg activation blocks development and reduces established neuropathic pain in rats. Neuropharmacology 70: 236-246: 2013
Nasirinezhad, F., S. Gajavelli, B. Pridy, S. Jergova, J.E. Zadina, J. Sagen.Viral vectors encoding endomorphins and serine histogranin attenuate neuropathic pain symptoms after spinal cord injury in rats. Mol Pain 11: 2, 2015. http://www.molecularpain.com/content/11/1/2
Aicher, S.A., Mitchell, J.L., Swanson, K.C., Zadina, J.E., 2003. Endomorphin-2 axon terminals contact mu-opioid receptor-containing dendrites in trigeminal dorsal horn. Brain Res. 977:190-8.
Wang, Q.P., Zadina , J.E., Guan, J.L., Kastin, A.J., Shioda, S., 2003. Electron microscopic examination of the endomorphin 2-like immunoreactive neurons in the rat hypothalamus. Brain Res. 969:126-34.
Greenwell, T.N., Zangen, A., Martin-Schild, S., Wise, R.A., Zadina, J.E., 2002. Endomorphin-1 and -2 immunoreactive cells in the hypothalamus are labeled by fluoro-gold injections to the ventral tegmental area. J. Comp. Neurol. 454:320-8.
Abbadie, C., Rossi, G.C., Orciuolo, A., Zadina, J.E., Pasternak, G.W., 2002. Anatomical and functional correlation of the endomorphins with mu opioid receptor splice variants. Eur. J. Neurosci. 16:1075-82.
Zadina, J.E., 2002. Isolation and distribution of endomorphins in the central nervous system. Jpn J Pharmacol. 89:203-8.
Zangen, A., Ikemoto, S., Zadina, J.E., Wise, R.A., 2002. Rewarding and psychomotor stimulant effects of endomorphin-1: anteroposterior differences within the ventral tegmental area and lack of effect in nucleus accumbens. J. Neurosci. 22:7225-33.
Wang, Q.P., Zadina, J.E., Guan, J.L., Kastin, A.J., 2002. Funahashi H, Shioda S. Endomorphin-2 immunoreactivity in the cervical dorsal horn of the rat spinal cord at the electron microscopic level. Neuroscience 113:593-605.
Kastin, A.J., Fasold, M.B., and Zadina, J.E., 2002. Endomorphins, Met-enkephalin, Tyr-MIF-1, and the P-glycoprotein efflux system. Drug Metab. Dispos. 30:231-4.
Martin-Schild, S.A., Gerall, A.A., Kastin, A.J. and Zadina, J.E. Differential distribution of endomorphin-1 and endomorphin-2-like immunoreactivities in the CNS of the rodent. J. Compar. Neurology 405:450-471, 1999.
Zadina, J.E., Hackler, L., Ge, L.-J., and Kastin, A.J. A potent and selective endogenous agonist for the µ-opiate receptor. Nature 386:499-502, 1997.