Pharmacology and Neurochemistry of Apomorphine*

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This chapter discusses the pharmacology and neurochemistry of apomorphine. Apomorphine was first employed as a powerful emetic agent. Apomorphine can be obtained by the acid-catalyzed rearrangement of morphine and by total synthesis. The hydrochloride forms colorless crystals that readily undergo superficial oxidation and assume a greenish tinge. Apomorphine solutions in water are unstable, turning green upon exposure to light and to air oxygen. Oxidation of apomorphine is much slower in acidic media. These properties of apomorphine explain the current addition of ascorbic acid to apomorphine solutions. The preparation of apomorphine by the acid-catalyzed rearrangement of morphine results in the retention of the configuration at the C6a chiral center leading to the corresponding (–)-isomer. Apomorphine has been measured in biological samples by spectrophotometric and fluorimetric methods and by fluorescence quenching after chromatographic separation. Apomorphine is metabolized by O-glucuronidation, O-methylation, and, probably, by N-demethylation. Apomorphine is methylated in vitro when incubated with rat liver soluble fraction in the presence of S-adenosylmethionine as methyl donor. This reaction is carried by the enzyme COMT.

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    *

    Much of the work reported herein was supported by grants from the Consiglio Nazionale delle Richerche, Rome.

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