Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder
| Autor: | Michael A. Fuller, Lesley B. Pickford, Ann C. Neale, F. Gerard Moeller, Crystal L. Carbone, Kirsten Z. Reiman, Jason B. Jayroe, Noelle C. Anastasio, Richard De La Garza, Tod A. Harper, Gaylyn J. Holstein, Stephen I. Bandak, Marcy J. Bubar, Thomas F. Newton, David L. Ware, Kathryn A. Cunningham |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Cmax Dopamine beta-Hydroxylase Pharmacology Placebo Cardiovascular System Article chemistry.chemical_compound Cocaine-Related Disorders Pharmacotherapy Pharmacokinetics Double-Blind Method Humans Enzyme Inhibitors Adverse effect Biological Psychiatry Pain Measurement Psychiatric Status Rating Scales Analysis of Variance Dose-Response Relationship Drug Imidazoles Thiones chemistry Nepicastat Cocaine use Female Analysis of variance Psychology Reinforcement Psychology Follow-Up Studies |
| Zdroj: | Progress in neuro-psychopharmacologybiological psychiatry. 59 |
| ISSN: | 1878-4216 |
| Popis: | In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxylase (DβH) 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 160 mg) concurrent with intravenous (IV) cocaine (0, 10, 20 and 40 mg) 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 (0 mg), 80 mg of nepicastat or 160 mg 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. |
| Databáze: | OpenAIRE |
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