Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition
Schmidt, Werner J.
Full recordShow full item record
AbstractIn the current study we compared the potency of the selective metabotropic glutamate receptor (mGluR1) antagonist A-841720 (7-Azepan-1-yl-4-dimethylamino-7H-9-thia-1,5,7-triaza-fluoren-8-one) in rodent models of pain with its effects in models of learning and memory, to obtain information regarding the therapeutic window of this compound. A-841720 significantly reduced formalin-induced behaviours and complete Freund's adjuvant (CFA)-induced tactile allodynia, starting at doses of 1 and 10 mg/kg, respectively. At the dose of 3 mg/kg, however, A-841720 significantly reduced the percentage of spontaneous alternations in a radial-maze task. In contextual-fear conditioning, A-841720, given at the dose of 10 mg/kg before acquisition, significantly reduced freezing behaviour tested 24 h later. In the same task, repeated treatment for 5 days did not reduce the impairing effect of the challenge dose, indicating a lack of tolerance development. In a passive-avoidance task, A-841720 at 10 mg/kg administered before acquisition, significantly reduced the latency to enter the dark box on the retention test. Given that complete Freund's adjuvant is a better measure of analgesia, these results indicate that the selective mGluR1 antagonist A-841720 has analgesic potential in a dose range at which it also produces memory impairments. This diminishes its therapeutic potential for the treatment of chronic pain.
Morè, Lorenzo, Gravius, Andreas, Pietraszek, Malgorzata, Belozertseva, Irina, Malyshkin, Andrey, Shekunova, Elena, Barberi, Caroline, Schaefer, Daniela, Schmidt, Werner J. and Danysz, Wojciech (2007) Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition. Behavioural Pharmacology , 18 (4). pp. 273-281. doi:10.1097/FBP.0b013e3281f19c18 <http://dx.doi.org/10.1097/FBP.0b013e3281f19c18>