1. Dear Drugs-Forum readers: We are a small non-profit that runs one of the most read drug information & addiction help websites in the world. We serve over 4 million readers per month, and have costs like all popular websites: servers, hosting, licenses and software. To protect our independence we do not run ads. We take no government funds. We run on donations which average $25. If everyone reading this would donate $5 then this fund raiser would be done in an hour. If Drugs-Forum is useful to you, take one minute to keep it online another year by donating whatever you can today. Donations are currently not sufficient to pay our bills and keep the site up. Your help is most welcome. Thank you.
    PLEASE HELP

D2 Receptor Partial Agonists: Treatment of CNS Disorders of Dopamine Function

D2 Receptor Partial Agonists: Treatment of CNS Disorders of Dopamine Function

  1. Anonymous
    Curr Top Med Chem. 2008;8(12):1068-88.
    Kehne JH, Andree TH, Heinrich JN.

    A remarkable diversity of psychiatric and neurological disorders have been associated with dysfunction of
    dopamine (DA)-containing neurons, including schizophrenia, bipolar disorder (BD), Parkinson’s disease (PD), and
    restless legs syndrome (RLS). In such disorders, transmission in discrete DA pathways may range from hypoactivation to
    hyperactivation of DA receptors, particularly those of the D2 subtype, providing the rationale for treatment approaches
    that activate or block D2 receptors, respectively. However, full agonists or pure D2 receptor antagonists may not be
    optimal therapeutic approaches for their respective disorders for a number of reasons, including an inability to restore the
    aberrant DA pathways to a normal level of basal tone. D2 receptor partial agonists (D2PAs) are proposed to stabilize
    activity in DA pathways by dampening excessive (and/or by restoring deficient) D2 receptor stimulation thereby
    shepherding DA neurons back to a desired level of basal activity. Stabilizing aberrant DA activity without disrupting nondysfunctional
    DA neurons may provide a potentially improved approach for treating DA disorders. The status of DA
    D2PAs and their potential application to schizophrenia, BD, PD, and RLS is reviewed. Preclinical and clinical evidence
    supports the idea that dysfunctions of D2 receptors contribute to these CNS disorders. Diseases in which both hyper- and
    hypofunction of DA pathways are present may be particularly promising, and challenging, targets for D2PAs.
    Furthermore, different DA disorders may respond optimally to D2PAs with differing levels of intrinsic activity, with “DA
    deficiency” diseases responding more effectively to higher intrinsic activity D2PAs than “DA hyperactivation” diseases.
    Overall, current evidence supports the conclusion that D2PAs have significant potential as improved CNS therapies
    relative to classic full agonists and antagonists at D2 receptors.