PubMed · 7045980
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J W Tilley, M J Kramer. 1981. Aminoadamantane derivatives.. https://doi.org/10.1016/s0079-6468(08)70315-1
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Striatal glutamatergic inputs are known to participate in the modulation of dopaminergic transmission. Accordingly, the non-competitive N-methyl-D-aspartate receptor antagonists memantine and amantadine increase striatal dopamine levels, the latter being widely used in Parkinson's disease therapy. Based on our previous work revealing increased function of dopamine receptors and dopamine transporter after amantadine treatment, we studied the effects of repeated memantine administration on dopaminergic neurotransmission. On rat striatal membranes, dopamine-stimulated [(35)S]GTPgammaS binding was significantly reduced (20%) after 2 days injection with memantine (20 mg/kg per day, i.p.) but not after longer treatments (4 or 7 days). Evaluation of [(3)H]SCH 23390 and [(3)H]spiperone specific bindings only revealed a significant increase in D1 receptor density after 4 or 7 days treatment. Finally, none of these treatments were found to change the activity of the neuronal dopamine transporter in striatal synaptosomes. This shows that amantadine and memantine differentially affect striatal dopaminergic transmission, which could indicate that these two related aminoadamantanes display distinct pharmacodynamic properties.
Recent evidence suggests that agmatine, an endogenous polyamine metabolite, might be an important neurotransmitter in central nervous system and has potential as a treatment of pain. The aim of our study was to evaluate the effect of agmatine on allodynia in two experimental neuropathic pain models, the spinal nerve ligation (SNL) model and the streptozocin (STZ)-induced diabetic neuropathy in rats, and to determine if the N-methyl-D-aspartate (NMDA) receptor antagonists and the nitric oxide synthase (NOS) inhibitors influence this effect of agmatine. Nerve injury was produced by tight ligation of the left L5 and L6 spinal nerves, and diabetic neuropathy is induced with the injection of a single dose of STZ; these procedures resulted in tactile allodynia in the hindpaw. Tactile allodynia was detected by application of von Frey filaments to the plantar surface of the foot. Agmatine reduced mechanical allodynia with its higher doses. Dizocilpine maleate (MK-801), a NMDA receptor antagonist, and the NOS inhibitors, N(G)-nitro-L-arginine methyl ester and 7-nitroindazole, did not influence the antiallodynic effect of agmatine. These results suggest that agmatine has an antiallodynic effect in both spinal nerve ligation and diabetic models and may be a promising drug in the treatment of neuropathic pain.