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Serotonin 5‐HT 2C Receptor of the Rat Detrusor Muscle: Evaluation of the Atypical Antipsychotics Olanzapine and Ziprasidone on the Isolated Rat Detrusor Muscle
Author(s) -
Morris Michelle,
GossellWilliams Maxine,
Nwokocha Chukwuemeka
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1023.5
Subject(s) - ziprasidone , olanzapine , serotonin , 5 ht receptor , detrusor muscle , serotonergic , medicine , chemistry , endocrinology , pharmacology , receptor , urinary bladder , schizophrenia (object oriented programming) , psychiatry
Background Atypical antipsychotics are preferentially prescribed over typical agents for greater efficacy in treating symptoms associated with schizophrenia and related psychoses. However, these antipsychotics have been found to reduce bladder function in patients. Antagonism of serotonin (5‐HT) receptor, 5‐HT 2C has been implicated as the cause. An in‐vitro preparation using the isolated rat detrusor muscle may be used to determine the effect of atypical agents Olanzapine and Ziprasidone on bladder contraction. Method: Bladders isolated from male Sprague Dawley rats (250–350g), were divided into longitudinal strips and immersed in Kreb's solution with carbogen (95% O 2 :5% CO 2 )at 37 0 C. After equilibration at 0.5g tension, the strips were stimulated with electric field stimulation (EFS) while adding 5‐HT (0.01‐30 µM and 0.1 nM‐1 µM) cumulatively at half‐log concentrations. A control concentration‐response curve (CRC) was constructed after which another CRC was constructed in the presence of Olanzapine (0.3nM‐3 µM) and Ziprasidone (0.001 nM‐1 nM) during EFS. Results: 5‐HT caused concentration dependent potentiation of EFS induced contractions and therefore may be a co‐regulator of micturition with ACh. Olanzapine (P蠄0.00) and Ziprasidone (P蠄0.00) significantly inhibited 5‐HT potentiated contractions in a concentration dependent manner. Conclusions The results suggest that atypical agents Olanzapine and Ziprasidone have potential to cause urinary retention. This effect may be due to affinity for 5‐HT receptors in the bladder. Funding: UWI, Office of Graduate Studies & Research