Neuroscience 2002 Abstract
| Presentation Number: | 830.14 |
|---|---|
| Abstract Title: | Novel, centrally-acting, non-imidazole H3 receptor (H3R) antagonists enhance cognition in rats. |
| Authors: |
Fox, G. B.*1
; Pan, J. B.1
; Lewis, A.1
; Faghih, R.1
; Esbenshade, T. A.1
; Black, L.1
; Bennani, Y. L.1
; Decker, M. W.1
; Hancock, A. A.1
1Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Lake County, IL |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - G-Protein Linked Receptors -- Other |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Neurotransmitters<br />-- Other |
| Session: |
830. G-protein linked receptors II Poster |
| Presentation Time: | Thursday, November 7, 2002 9:00 AM-10:00 AM |
| Location: | Hall A2-B3 C-36 |
| Keywords: | HISTAMINE, LEARNING AND MEMORY, PASSIVE AVOIDANCE, ATTENTION |
Pharmacological blockade of central H3Rs with ciproxifan, thioperamide and GT-2331 enhances attention and cognition in rodents. However, these compounds share the imidazole moiety with the endogenous agonist, histamine, and have high affinity for several additional receptors. Here, we present in vivo behavioral data for 2 novel and selective, non-imidazole H3R antagonists with improved safety indices (for in vitro data, see accompanying poster by Yao et al., SFN 2002). A-304121 and A-317920, 2 novel piperazine amides, were tested in a 5-trial, repeated acquisition, inhibitory avoidance test in the rat pup. Significantly improved performance was observed following administration of A-304121 (10 mg/kg sc) or A-317920 (3 mg/kg sc), with efficacy comparable to reference H3R blockers thioperamide (10 mg/kg sc), ciproxifan (3 mg/kg sc), and GT-2331 (1 mg/kg sc). Relative therapeutic indices (TIs) of 30 and 42 were estimated for A-304121 and A-317920, respectively, from observation of CNS adverse effects in mouse Irwin studies compared to potency in inhibitory avoidance, which were superior to TIs of 8, 10 and 18 observed for thioperamide, ciproxifan and GT-2331, respectively. A-304121 (3, 10 mg/kg sc) also significantly enhanced performance in a social recognition test of short-term memory in the adult rat. In summary, the novel and H3R-selective piperazine amides A-304121 and A-317920 are efficacious in in vivo models of cognition.
Supported by Abbott Laboratories
For-profit corporation
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
Copyright © 2002-2026 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
