Effect of novel phenothiazine derivatives on brain dopamine in Wistar rats

Abstract

Abstract Background Neurotransmitters are involved in several functions in the brain and the body of living things. Changes in the level of neurotransmitters in the brain are associated with several illnesses. Some of the drugs are controlling the neurotransmitter by adjusting the level in the brain and are exclusively used in the treatment of psychological disorders. The purpose of the study was to find out the effect of novel synthesised phenothiazine derivatives (GC1, GC2 and GC8) either alone (7.5 mg/kg or 15 mg/kg, oral) or in combination with amphetamine on the experimental animals. Results Dopamine level in rat brain was estimated by a spectroscopic method using the UV-visible double beam spectrophotometer at 735 nm. The results revealed that these derivatives blocked the brain dopamine level significantly. The compound GC8 (15 mg/kg) significantly reduced the level of dopamine (0.151 ± 0.04, 0.284 ± 0.03) as similar to that of a standard drug. Furthermore, compounds GC2 (15 mg/kg) and GC1 (15 mg/kg) exhibited a varying level of dopamine inhibition level and have been found at 0.203 ± 0.06 μg/ml, 0.302 ± 0.04 μg/ml, 0.234 ± 0.02 μg/ml and 0.318 ± 0.07 μg/ml, respectively, after the administration of these derivatives either alone or in combination with amphetamine. Conclusions The study revealed that the compound 2-amino-6-(3-hydroxy-4-methyl phenyl) pyrimidine-4-yl) (7-chloro-10-(3- (N, N-dimethylamino) propyl)-10H-phenothiazine-3-yl) methanone (GC8, 15 mg/kg) extensively reduced the dopamine level. The order of dopamine-inhibiting effect of the selected compound was found to be GC8 > GC2 > GC1. The increased body weight and relative brain-body weight were also observed in the tested animals due to more intake of food and fluid retention. Graphical abstract