Möglichkeiten pharmakologischer Interventionen: Impfstoffe und Pharmakotherapie in der Suchtbehandlung der Zukunft

Zusammenfassung

In den letzten Jahren ist es uns gelungen neue Tiermodelle zu entwickeln, die viele Aspekte von Alkoholismus und Opiatabhängigkeit darstellen (nach DSM-IV). Mit Hilfe des Alkoholtrinkmodells konnte die Wirksamkeit von Acamprosat (Campral®) und Naltrexon (Revia™) nachgewiesen werden. Mit weiteren verhaltenspharmakologischen Untersuchungen und elektrophysiologischen / molekularbiologischen Methoden konnten wir den Wirkmechanismus dieser Substanzen weitgehend aufklären: Naltrexon blockiert Opiatrezeptoren auf Neuronen des mesolimbischen Belohnungssystems und hemmt dabei die akuten wie auch konditionierten Verstärkereigenschaften von Alkohol und Opiaten („positives Craving”), während Acamprosat vorwiegend mit dem glutamatergen N-Methyl-D-Aspartat-(NMDA)-System interagiert und zu deutlichen Veränderungen genomisch vermittelter Prozesse führt. Acamprosat unterdrückt dabei sowohl akute als auch konditionierte Entzugssymptome („negatives Craving”). Sollte es nun weiterhin möglich werden, bei alkoholkranken Patienten zu unterscheiden zwischen denen, die positives Craving, und solchen, die negatives Craving (o. beides) nach einer „Cue exposure” verspüren, so könnte eine zielgerichtete Pharmakotherapie eingesetzt werden (individuell adaptierte Pharmakotherapie). Alternativ hierzu werden verschiedene Aspekte der Drogenimmunisierung diskutiert.

Possibilities of Pharmacological Interventions: Vaccines and Pharmacotherapy in the Addiction Treatment of the Future

New animal models of alcoholism and opiate addiction have been developed. Rats derived from our long-term alcohol drinking model show certain symptoms also seen in human alcoholics. Recently, naltrexone and acamprosate have been approved in several countries as relapse prevention in weaned alcoholics. We examined the efficacy of these compounds in our drinking model and tried to elucidate their putative mode of action. The opioid receptor antagonist naltrexone reduced the alcohol-deprivation effect in long-term ethanol experienced rats. It is suggested that naltrexone reduces ethanol reinforcement and conditioned cue reactivity most likely via a blockade of opioid receptors („positive craving”). The repeated administration of acamprosate also reduces the alcohol-deprivation effect. Acamprosate interferes with several symptoms of withdrawal most likely via a normalisation of neuronal hyperactivity. It is suggested that acamprosate reduces neuronal hyperactivity during protracted withdrawal and conditioned withdrawal responses via a selective influence upon NMDA-receptor composition („negative craving”). In the near future we are aiming for an indivual adapted pharmacotherapy where patients who show positive and negative craving, respectively, will be matched to the appropriate treatment. Alternatively to these pharmacological intervention strategies the possibility of drug immunization will be discussed.

Schlüsselwörter

Sucht - Rückfall - Craving - Tiermodelle - Alkohol - Opiate - Acamprosat - Naltrexon - Drogenimmunisierung

Key words

Addiction - Relapse - Craving - Animal Models - Alcohol - Opioids - Acamprosate - Naltexone - Drug Immunization

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