Related Experiment Videos
Formation of alpha-methyldopamine ("Catecholamphetamine") from p-hydroxyamphetamine by rat brain microsomes
Pharmacology
|January 1, 1979
Summary
Amphetamine metabolism produces p-hydroxyamphetamine, which is further converted to catecholamphetamine in the rat brain. This catechol metabolite may contribute to amphetamine tolerance during chronic use.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Amphetamine is a psychotropic drug metabolized in the liver and brain.
- A key metabolite, p-hydroxyamphetamine, is taken up by synaptosomes.
- The potential for further metabolism of p-hydroxyamphetamine to a catecholamine is unknown.
Purpose of the Study:
- To investigate if p-hydroxyamphetamine can be metabolized into a catecholamine.
- To develop a method for detecting catecholamphetamine formation.
Main Methods:
- Development of a sensitive radioenzymatic assay.
- Coupling catecholamphetamine formation to O-methylation using catechol-O-methyltransferase and [3H]-methyl-S-adenosylmethionine.
- Incubation of rat brain microsomes with p-hydroxyamphetamine.
Main Results:
- Rat brain microsomes possess a cytochrome P-450-dependent monooxygenase.
- This enzyme synthesizes catecholamphetamine from p-hydroxyamphetamine.
- The formation of this catechol metabolite was confirmed.
Conclusions:
- p-Hydroxyamphetamine is a precursor to catecholamphetamine in the rat brain.
- The synthesis is mediated by a cytochrome P-450 enzyme.
- This metabolic pathway may play a role in amphetamine tolerance.