The aim of this study was to design drug-like molecules with multiple neuroprotective mechanisms which would ultimately inhibit N-methyl-D-aspartate (NMDA) receptors, block L-type voltage gated calcium channels (VGCC) and inhibit apoptotic processes as well as the monoamine oxidase-B (MAO-B) enzyme in the central nervous system. These types of compounds may act as neuroprotective and symptomatic drugs for disorders such as Alzheimer's and Parkinson's disease. In designing the compounds we focused on the structures of rasagiline and selegiline, two well known MAO-B inhibitors and proposed neuroprotective agents. Based on this consideration, the compounds synthesised all contain the propargylamine functional group of rasagiline and selegiline or a derivative thereof, conjugated to various polycyclic cage moieties. Being non-polar, these polycyclic moieties have been shown to aid in the transport of conjugated compounds across the blood-brain barrier, as well as cell membranes and have secondary positive neuroprotective effects. All novel synthesised polycyclic derivatives proved to have significant anti-apoptotic activity (p < 0.05) which was comparable to the positive control, selegiline. Four compounds (12, 15 and 16) showed promising VGCC and NMDA receptor channel inhibitory activity ranging from 18% to 59% in micromolar concentrations and compared favourably to the reference compounds. In the MAO-B assay, 8-phenyl-ethynyl-8-hydroxypentacycloundecane (10), exhibited MAO-B inhibition of 73.32% at 300 μM. This compound also reduced the percentage of apoptotic cells by as much as 40% when compared to the control experiments.