Comments from a psychiatrist – NOT clinical advice.

Home Forums Alternatives to Modecate Comments from a psychiatrist – NOT clinical advice.

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    Many previously stable patients are finding it difficult to find a suitable alternative to fluphenazine. When a person has been on a high-potency medication for many years, secondary changes may take place in their brain which may make it difficult for other agents to successfully replace them. Dopamine receptor supersensitivity has been suggested as one such possible adaptation, and there is evidence that such adaptations may persist.

    For one of my patients the fluphenazine was replaced with flupenthixol depot but these medications are quite dissimilar in their receptor activity. Fluphenazine is a phenothiazine compound, and it was known as a ‘high-potency’ agent, with strong antagonist activity at the D2 receptor compared to its effect on other receptor types due to a piperazine side chain at position 10. By contrast, flupenthixol is a thioxanthe compound and is a ‘low potency’ agent, and the sedative side effects comparatively outweigh the direct antipsychotic activity.

    The closest related medication still obtainable (at least in Australia) would be periciazine (Neulactil), but this is still a lower potency agent with a piperadine side chain. An alternative would be to use an alternative high-potency agent such as the butyrophenone haloperidol which has a broadly similar receptor profile and is widely available, often as a depot agent. The risks of side effects such as movement disorders are not significantly higher than for the Modecate, and hopefully (apart from the risk of emergent tardive dyskinesia) can be managed with benztropine or similar agents. See below – M is for muscarinic receptor (cholinergic system).

    Receptor Profile D2 5HT2 M A-1 adrenergic Antihistamine

    Fluphenazine ++++ ++ + + ++
    Haloperidol ++++ ++ + + +

    #442 Reply


    I note the table came out very odd – here is a rewrite which should make more sense.

    D2 Activity Fluphenazine ++++ Haloperidol ++++
    5HT2 Activity Fluphenazine ++ Haloperidol ++
    Muscarinic Activity Fluphenazine + Haloperidol +
    Alpha-1 adrenergic Activity Fluphenazine + Haloperidol +
    Antihistamine Activity Fluphenazine ++ Haloperidol +

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