In contrast to conventional
opioid analgesics, antagonists acting at the
N-methyl-d-aspartate (
NMDA) subtype of
glutamate receptors are capable of suppressing
pain-related phenomena in
chronic pain models while having little or no effect on acute nociception. One of the few clinically used
NMDA receptor antagonists,
memantine, differs from prototypic antagonists with psychotomimetic activity such as
phencyclidine and (+)
MK-801, in showing lower receptor affinity, faster unblocking kinetics and stronger voltage-dependency. Recently, a series of novel amino-alkyl-
cyclohexanes was reported to interact with
NMDA receptors in a manner similar to that of
memantine. The present study aimed to evaluate the effects of these compounds as well as (+)
MK-801 and
memantine in two rat models of
chronic pain and the rotarod test. Unlike (+)
MK-801 and
memantine, most of the tested compounds were inactive against
tactile allodynia induced by sciatic nerve
ligation. On the other hand, all tested drugs were found to inhibit
formalin-induced grooming behavior-a model of
chronic pain induction. In agreement with previous reports on the effects of
NMDA receptor antagonists in similar assays, the late phase seemed to be inhibited to a greater extent than the early phase. For all tested compounds, inhibition of
formalin-induced behaviors occurred at dose levels that were also producing significant motor deficits (rotarod test). These results confirm low efficacy of acute administration of
NMDA receptor antagonists in the models of established
pain states. Thus, studies on the prevention and management of chronic
pain should focus on preemptive or long-term administration of
NMDA receptor antagonists.