| Author |
De La Garza, Richard Bubar, Marcy J. Carbone, Crystal L. Moeller, F. Gerard Newton, Thomas F. Anastasio, Noelle C. Harper, Tod A. Ware, David L. Fuller, Michael A. Holstein, Gaylyn J. Jayroe, Jason B. Bandak, Stephen I. Reiman, Kirsten Z. Neale, Ann C. Pickford, Lesley B. Cunningham, Kathryn A. |
| Description |
Author Affiliation: De La Garza R ( Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States. Electronic address: rg12@bcm.edu.); Bubar MJ ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States.); Carbone CL ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States.); Moeller FG ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States); Newton TF ( Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States.); Anastasio NC ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States); Harper TA ( Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States.); Ware DL ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States); Fuller MA ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States); Holstein GJ ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States); Jayroe JB ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States); Bandak SI ( Biotie Therapies, Inc. (formerly Synosia Therapeutics), South San Francisco, CA, United States.); Reiman KZ ( Biotie Therapies, Inc. (formerly Synosia Therapeutics), South San Francisco, CA, United States.); Neale AC ( Biotie Therapies, Inc. (formerly Synosia Therapeutics), South San Francisco, CA, United States.); Pickford LB ( Biotie Therapies, Inc. (formerly Synosia Therapeutics), South San Francisco, CA, United States.); Cunningham KA ( Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States) |
| Abstract |
In the present study, we tested the hypothesis that the potent and selective dopamine-ß-hydroxylase (DßH) inhibitor nepicastat would have minimal effects on cardiovascular and pharmacokinetic parameters associated with cocaine administration and would reduce the positive subjective effects produced by cocaine. We conducted a double-blind, placebo-controlled, inpatient study of oral nepicastat (0, 80 and 160mg) concurrent with intravenous (IV) cocaine (0, 10, 20 and 40mg) in non-treatment seeking participants who metcriteria for cocaine use disorder. Safety analyses revealed that nepicastat was well-tolerated and there were no differences in adverse events observed after nepicastat plus cocaine vs. cocaine alone. In addition, the pharmacokinetic properties of cocaine administration were not altered by nepicastat treatment. Cocaine-induced cardiovascular and subjective effects were evaluated for completers in the cohort randomized to nepicastat (n=13) using a within-subjects statistical analysis strategy. Specifically, the cardiovascular and subjective effects of cocaine were assessed in the presence of placebo (0mg), 80mg of nepicastat or 160mg of nepicastat on study Days 4, 8 and 12, respectively. Analyses revealed a main effect of nepicastat to reduce several cocaine-induced positive subjective effects. Taken together, these data indicate that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder. |
