Fig. 4: Pharmacological targets within the pre- and post-synapse.
From: Impact of distinct neurotransmitter release modes on neuronal signaling
Molecular targets of several clinically relevant neuro- and psychotropic drugs. Presynaptic targets: (1) Voltage-gated sodium channels: Blockers like carbamazepine, lamotrigine, riluzole, and topiramate reduce neuronal excitability by inhibiting action potential propagation. (2) Voltage-gated calcium channels (VGCCs): Gabapentin and pregabalin bind to the α2δ auxiliary subunit of VGCCs. (3) Synaptic vesicle protein 2A (SV2A): Levetiracetam and brivaracetam bind to SV2A, a protein involved in regulating the function and trafficking of the synchronous calcium sensor Syt-1. (4) SNARE complex: Botulinum toxin proteolytically cleaves SNARE proteins (e.g., SNAP-25, VAMP2), directly preventing vesicle fusion. Other common presynaptic targets include the serotonin reuptake transporter (SERT), monoamine oxidase (MAO), and the vesicular monoamine transporter 2 (VMAT2). Postsynaptic targets: (5) NMDA receptors (NMDARs): Antagonists like amantadine, ketamine, felbamate, and memantine block NMDAR-mediated currents. (6) AMPA receptors (AMPARs): Antagonists like perampanel and topiramate block AMPAR-mediated currents. Other common postsynaptic targets include the 5-HT1A receptor, GABAA receptors, and dopamine (D2) and serotonin (5-HT2A) receptors.
