HARCP

HEROIN ADDICTION AND
RELATED CLINICAL PROBLEMS

The official journal of
EUROPAD - European Opiate Addiction Treatment Association
WFTOD - World Federation for the Treatment of Opioid Dependence
Editor: Icro Maremmani, MD - Pisa, Italy, EU
Associate Editors:
Thomas Clausen, MD - Oslo, Norway
Pier Paolo Pani, MD - Cagliari, Italy, EU
Marta Torrens, MD - Barcelona, Spain, EU
Statistical Editor:
Mario Miccoli, PhD - Pisa, Italy, EU

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Heroin Addiction and Related Clinical Problems: 2009, 11, 3 (pages: 11 - 28)

Pharmacology and Neurochemistry of Methadone

Vendramin A., Sciacchitano A. M.

Summary: Contrary to what might be thought initially, the pharmacology of methadone is only partly known, and current research continues to investigate into its distinctive aspects. Clinical evidence provides key guidance to pharmacological research on the opiate system; on the other hand, evolving expectations from therapeutic drugs or putative agents for addiction treatment provide a key incentive to the broadening of pharmacological knowledge. Apart from the classic description of receptorial opioid agonism, narcotic blockade and tolerance/withdrawal dynamics, some crucial issues need to be clarified in a comprehensive way. For instance, studies have proved the importance of metabolic polymorphism in treatment planning and offered interpretations of apparent resistance to normal dosages, so authorizing the employment of high dosages on a sound pharmacological basis. Also, dosages should not be regarded as stable through time, especially in the first few months, and clinicians may schedule dose variations that take into account such expected variations while pursuing stabilization. Methadone's action profile in the central nervous system is not exclusively based on opioid receptors, and a thorough knowledge of its 'collateral' effects may explain its beneficial action against specific psychopathological abnormalities. The role of the inactive enantiomer in the context of racemous methadone's tolerability and action profile has also been outlined. Lastly, some of the therapeutic effects of methadone endure without being neutralized by the emergence of tolerance; one of these is its crucial anticraving property. In order to clarify this issue, the mechanisms of cell membrane endocytosis and signal transduction have been illustrated and compared between different opiates.

 

EUROPAD - European Opiate Addiction Treatment Association
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