[Effect of neuroleptics on tyrosine hydroxylase from rat hypothalamus synaptosomes]

A study was made of the effect of a number of neuroleptics of various chemical structure of tyrosine-hydroxilase isolated from the synaptosomes of rat hypothalamus. A direct spectrophotometric method of determination of the activity of the enzyme was used; it was based on measurement of the absorbence at 335 nm (at the isobestic point for oxidized forms of a synthetic cofactor 6,7-dimethyl-5,6,7,8-tetrahydropterine). At the tyrosine concentration of 0.15 muM haloperidol, haloanizon, and fluorophenazin were found to increase, and triperidol, droperidol and carbidin -- to decrease the initial rate of thyrosinehydroxilase reaction. All the neuroleptics under study proved to be capable of eliminating the substrate inhibition of the enzyme occurring with a rise of tyrosine concentration to 0.3 mM. The KM value for tyrosine failed to alter with the action of neuroleptics. The effect of neuroleptics was assumed to be of allosteric nature.