Abstract

The earliest reports of flumazenil's antagonist effects at the benzodiazepine receptor did not report significant intrinsic activity. In contrast to these early reports, more recent studies have reported agonist, and even inverse agonist, effects of flumazenil across several measures and species. The purpose of the present study is to characterize the discriminative stimulus and self-reported effects of flumazenil in humans. Six subjects learned to discriminate flumazenil (0.56 mg/70 kg; iv) from saline. In addition, substitution tests with various doses of flumazenil (0, 0.10, 0.32, 0.56 and 1.0 mg/70 kg) demonstrated dose- dependent increases on several self-report measures sensitive to sedative- like effects (e.g., PCAG subscale of the ARCI, sedative rating on the adjective rating scale), as well as increased ratings of """"""""high"""""""" and """"""""strength of drug effect"""""""". Taken together, these results support other research suggesting agonist effects of flumazenil. Future studies will focus on determining the specificity of flumazenil's agonist effects at the benzodiazepine receptor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000109-34
Application #
6277206
Study Section
Project Start
1997-12-01
Project End
1998-11-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
34
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Vermont & St Agric College
Department
Type
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405

  Publications

Scagnelli, Connor N; Howard, Diantha B; Bromberg, Mark B et al. (2018) Hydration measured by doubly labeled water in ALS and its effects on survival. Amyotroph Lateral Scler Frontotemporal Degener 19:220-231
Horne, Hisani N; Sherman, Mark E; Pfeiffer, Ruth M et al. (2016) Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease. Breast Cancer Res 18:24
Kien, C Lawrence; Matthews, Dwight E; Poynter, Matthew E et al. (2015) Increased palmitate intake: higher acylcarnitine concentrations without impaired progression of ?-oxidation. J Lipid Res 56:1795-807
Gierach, Gretchen L; Patel, Deesha A; Falk, Roni T et al. (2015) Relationship of serum estrogens and metabolites with area and volume mammographic densities. Horm Cancer 6:107-19
Albert, Kimberly; Pruessner, Jens; Newhouse, Paul (2015) Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle. Psychoneuroendocrinology 59:14-24
Bodelon, Clara; Heaphy, Christopher M; Meeker, Alan K et al. (2015) Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy. BMC Cancer 15:823
Morris, Erin A; Hale, Sarah A; Badger, Gary J et al. (2015) Pregnancy induces persistent changes in vascular compliance in primiparous women. Am J Obstet Gynecol 212:633.e1-6
Miller, Mark S; Bedrin, Nicholas G; Ades, Philip A et al. (2015) Molecular determinants of force production in human skeletal muscle fibers: effects of myosin isoform expression and cross-sectional area. Am J Physiol Cell Physiol 308:C473-84
Kien, C Lawrence; Bunn, Janice Y; Fukagawa, Naomi K et al. (2015) Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes. J Nutr Biochem 26:1599-606
Fox, James R; Gray, Weili; Koptiuch, Cathryn et al. (2014) Anisotropic tissue motion induced by acupuncture needling along intermuscular connective tissue planes. J Altern Complement Med 20:290-4

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