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    Mechanism of Action of Quetiapine

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    Thoha Albaar
    Quetiapine is a second-generation antipsychotic with affinity for D2, 5-HT2A, H1, alpha 1, and 5-HT1A receptors. Its mechanism of action is unknown but may involve reducing dopaminergic neurotransmission. Studies show a relationship between D2 receptor occupancy and antipsychotic effects, with 60-75% occupancy associated with efficacy. However, quetiapine occupies only 30% of D2 receptors at therapeutic doses. Kapur proposed the "kiss and run" hypothesis to explain this, suggesting quetiapine has rapid dissociation from D2 receptors. Quetiapine also has antagonist actions at 5-HT2A receptors and is a partial ag

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    Mechanism of Action of Quetiapine

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    Thoha Albaar
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    Quetiapine is a second-generation antipsychotic with affinity for D2, 5-HT2A, H1, alpha 1, and 5-HT1A receptors. Its mechanism of action is unknown but may involve reducing dopaminergic neurotransmission. Studies show a relationship between D2 receptor occupancy and antipsychotic effects, with 60-75% occupancy associated with efficacy. However, quetiapine occupies only 30% of D2 receptors at therapeutic doses. Kapur proposed the "kiss and run" hypothesis to explain this, suggesting quetiapine has rapid dissociation from D2 receptors. Quetiapine also has antagonist actions at 5-HT2A receptors and is a partial ag

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    quetiapine as a pschycotherapy

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    Quetiapine is a second-generation antipsychotic with affinity for D2, 5-HT2A, H1, alpha 1, and 5-HT1A receptors. Its mechanism of action is unknown but may involve reducing dopaminergic neurotransmission. Studies show a relationship between D2 receptor occupancy and antipsychotic effects, with 60-75% occupancy associated with efficacy. However, quetiapine occupies only 30% of D2 receptors at therapeutic doses. Kapur proposed the "kiss and run" hypothesis to explain this, suggesting quetiapine has rapid dissociation from D2 receptors. Quetiapine also has antagonist actions at 5-HT2A receptors and is a partial ag

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    458 views4 pages

    Mechanism of Action of Quetiapine

    Uploaded by

    Thoha Albaar
    Quetiapine is a second-generation antipsychotic with affinity for D2, 5-HT2A, H1, alpha 1, and 5-HT1A receptors. Its mechanism of action is unknown but may involve reducing dopaminergic neurotransmission. Studies show a relationship between D2 receptor occupancy and antipsychotic effects, with 60-75% occupancy associated with efficacy. However, quetiapine occupies only 30% of D2 receptors at therapeutic doses. Kapur proposed the "kiss and run" hypothesis to explain this, suggesting quetiapine has rapid dissociation from D2 receptors. Quetiapine also has antagonist actions at 5-HT2A receptors and is a partial ag

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    Quetiapine is a second-generation antipsychotic that acts as an antagonist at serotonin 5-HT2A and dopamine D2 receptors. It also acts as a partial agonist at 5-HT1A receptors. Its precise mechanism of action is unknown but it is thought to involve rapid dissociation from D2 receptors.

    The proposed mechanisms of action of quetiapine include 5-HT2A/D2 antagonism, 5-HT1A partial agonism, and having a higher affinity for 5-HT2A receptors than D2 receptors. Its affinity for 5-HT1A receptors is also proposed to contribute to its antidepressant effects.

    Quetiapine has affinity for D2, 5-HT2A, H1, alpha 1 and 5- HT1A receptors. Antagonism at H1 receptors is linked to sedative effects and weight gain, while alpha 1 antagonism can cause orthostatic hypotension.

    Author: Flavio Guzman, MD

    Psychiatrist
    Pharmacology Department
    University of Mendoza
    Argentina

    Quetiapine is a second-generation antipsychotic that has affinity for D2, 5-HT2A, H1, alpha 1 and 5-
    HT1A receptors. Its precise mechanism of action is unknown, but according to the dopamine
    theory of schizophrenia, antipsychotic effects might be related to the drug’s ability to reduce
    dopaminergic neurotransmission in the mesolimbic pathway.

    Quetiapine mechanism of action might involve rapid dissociation from D2 receptors.

    PET studies show that there is a relationship between D2 receptor occupancy and antipsychotic
    effects [1]. D2 receptor occupancy in the ranges of 60 % to 75% is associated with antipsychotic
    efficacy. Interestingly, quetiapine has been shown to occupy approximately 30% of D2 receptors
    at therapeutic doses [2].

    To explain the apparent discrepancy, Kapur proposed the “kiss and run” hypothesis. In a series of
    studies they found that in contrast to other antipsychotics, quetiapine had a more rapid “run-off”,
    or rapid dissociation, from D2 receptors [2].

    1
    This section is an illustrated representation of the most relevant pharmacodynamic properties of
    quetiapine.

    Putative mechanism of action of quetiapine involves 5-HT2A/D2 antagonism and 5-HT1A partial agonism.
    H1 and alpha 1 antagonism are linked to side effects.

    Quetiapine has antagonist actions at 5-HT2A receptors, one of the key properties of second-
    generation antipsychotics is that they have a high 5-HT2A/D2 ratio. Quetiapine has higher affinity
    for 5-HT2A receptors than for D2 receptors [3].

    Quetiapine, aripiprazole, asenapine and ziprasidone are partial agonists at 5-HT1A receptors. Affinity
    for this receptor is one of the proposed mechanisms of action of quetiapine’s antidepressant
    effects [4].

    Alpha 1 antagonism can cause orthostatic hypotension, this potential side effect can be prevented
    by slow dose titration.

    Quetiapine is a strong antagonist at H1 receptors. H1 antagonism is linked to sedative effects and


    weight gain [2].

    2
    This table shows Ki values for quetiapine at different neurotransmitter receptors. Ki is inversely
    proportional to affinity. This means that high Ki numbers suggest low affinity at a given receptor,
    while low Ki numbers are associated with high affinity.

    Receptor type Ki value (nM)

    D2 380

    5HT1A 390

    5HT2A 640

    5HT2C 1840

    D1 990

    D4 2020

    M1 37

    Alpha 1 A 22

    Alpha 2 A 2900

    H1 6.9

    Binding potency of quetiapine at different receptors. Modified from [5]

    3
    1. Kapur S, Zipursky R, Jones C, Remington G, Houle S. Relationship between dopamine D(2)
    occupancy, clinical response, and side effects: a double-blind PET study of first-episode
    schizophrenia. The American journal of psychiatry 2000;157:514-20.
    2. Schatzberg, AF, Nemeroff, C . The American Psychiatric Publishing Textbook of
    Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009.
    3. Tasman, A; Lieberman, J; Key, J; Maj, M. Psychiatry. 3rd ed. John Wiley & Sons, 2008
    4. Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL. N-
    desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist,
    as a putative mediator of quetiapine’s antidepressant activity. Neuropsychopharmacology :
    official publication of the American College of Neuropsychopharmacology 2008;33:2303-12.
    5. Brunton LB, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of
    Therapeutics. 12th ed. New York: McGraw-Hill; 2010.

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