The blood-brain barrier restricts the brain uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, amino acid-coupled liposomes bearing dopamine HCl were prepared to deliver the drug to the brain utilizing receptor-mediated transcytosis. Uncoupled liposomes were prepared by cast film method using phosphatidylcholine and cholesterol, whereas coupled liposomes were prepared using phosphatidylcholine, cholesterol, and glutamate stearylamine conjugate in the film. These liposomes were characterized for entrapment efficiency, vesicle size, shape, in vitro drug release, and in vivo studies. The in vitro drug release was analysed by using dialysis membrane. The vesicle size was found to increase upon coupling of liposomes, whereas percent entrapment efficiency was reduced from 38.89 +/- 1.94% to 34.15 +/- 1.70% after coupling of liposomes. The in vitro percent cumulative drug release studies exhibited 51.6% drug release for uncoupled liposome and 37.9% for coupled liposome at the end of 24 h. These selected formulations were subjected for in vivo performance, which was assessed by periodic measurement of drug (chlorpromazine)-induced catatonia in albino rats (Wistar strain) and fluorescence microscopy studies of the rat brain. The results were compared with plain dopamine HCl solution. Studies revealed that dopamine HCl can be effectively delivered to brain via glutamate-coupled liposomes, and results clearly indicated the superiority of the coupled liposomal formulation over the uncoupled formulation.