Substituted amphetamine derivatives. II. Behavioural effects in mice related to monoaminergic neurones

The effects of the amphetamine derivatives (+/-)-amphetamine (A), 2-, 3- and 4-chloroamphetamine (CA), 4-methylamphetamine (MA) and chlorphentermine (CP) in producing central stimulation (increase in motor activity), antagonism of the reserpine syndrome, potentiation of 1-dopa and 5-hydroxytryptophan (5HTP) responses in mice were investigated. The inhibitors of the membrane amine uptake despramine (DMI) and chlorimipramine (CI) were also included in the study. It was found that the order in central stimulating potency was A greater than 3-CA = 4-CA greater than MA greater than CP. 2-CA, DMI and CI decreased the motor activity. All the compounds potentiated the 1-dopa response with the order of activity: 4-MA greater than A greater than 2-CA = 3-CA = 4-CA = CI greater than or equal to DMI greater than CP. The decrease in motor activity (sedation) produced by reserpine was only reversed by A greater than or equal to 3-CA greater than 2-CA. alpha-Methyltyrosine but not parachlorophenylalanine, antagonized the reversal effect. Three of the compounds (3-CA, 4-CA and MA) produced head-twitches in the reserpinized mice. The 5-HTP syndrome was potentiated in order of potency by MA = 4-CA greater than CI greater than CP greater than 3-CA whereas A, 2-CA and DMI had no effect.