The clinical symptoms of Parkinson’s disease (PD) appear when dopamine (DA) concentrations in the striatum drops to around 20%. Simultaneous inhibitory effects on histamine H receptor (HR) and MAO B can increase DA levels in the brain. A series of compounds was designed and tested in vitro for human HR (h) affinity and inhibitory activity to human MAO B (hMAO B). Results showed different activity of the compounds towards the two biological targets. Most compounds had poor affinity for h (K > 500 nM), but very good inhibitory potency for hMAO B (IC < 50 nM). After further in vitro testing (modality of MAO B inhibition, permeability in PAMPA assay, cytotoxicity on human astrocyte cell lines), the most promising dual-acting ligand, 1-(3-(4-(tert-butyl)phenoxy)propyl)-2-methylpyrrolidine (13: hHR: K= 25 nM; hMAO B IC = 4 nM) was selected for in vivo evaluation. Studies in rats of compound 13, in a dose of 3 mg/kg of body mass, confirmed its antagonistic effects for HR (decline in food and a water consumption), decline in MAO B activity (>90%) in rat cerebral cortex (CTX), and an increase in DA content in CTX and striatum. Moreover, compound 13 caused a slight increase in noradrenaline, but a reduction in serotonin concentration in CTX. Thus, compound 13 is a promising dual-active ligand for the potential treatment of PD although further studies are needed to confirm this.