In vitro studies on the possible effects of 1-aminoadamantanes on the serotonergic system in M. Parkinson

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Abstract
Synaptosomes, synaptic vesicles, and membranes were isolated from rat brain homogenates by differential and density gradient centrifugation in sucrose. Synaptosomes incorporated serotonin (5-HT) with two different uptake mechanisms, high affinity: Kt1=47 nM and low affinity: Kt2=660 nM. Both uptake mechanisms are non-competitively inhibited by the potential antiparkinson drugs 1-aminoadamantane (amantadine, D 1: Ki1=57μM, Ki2=96μM) and 1-amino-3.5-dimethyladamantane (memantine, D 145: Ki1=97μM, Ki2=150μM). The incorporated 5-HT is released from Synaptosomes on incubation with high concentrations (0.5–5 mM) of the drugs or on electrical stimulation with rectangular pulses of alternating polarity. Subthreshold concentrations of these drugs (5–50μM) which are too low to liberate 5-HT increase the electrically stimulated release of 5-HT.—The effect of D 1, D 145, and electrical stimulation on DA release parallels the results observed with 5-HT. The uptake of 5-HT into isolated synaptic vesicles and the binding to isolated nerve ending membranes is non-competitively inhibited by 1-aminoadamantanes. D 145 inhibits the binding of 5-HT to membranes more effectively (Ki=0.95 mM) than its uptake into vesicles (Ki=1.2mM) contrasting with D 1 which is a weaker inhibitor affecting vesicular uptake (Ki=2.5 mM) slightly more than membrane binding (Ki=3.1 mM). The results obtained suggest that, in addition to other mechanisms like receptor stimulation, 1-aminoadamantanes may act in parkinsonian patients by enriching the transmitter content in the synaptic cleft.