Literature DB >> 21537940

Dipyridamole monotherapy in schizophrenia: pilot of a novel treatment approach by modulation of purinergic signaling.

Ikwunga Wonodi1, Hirekatur V Gopinath, Judy Liu, Helene Adami, L Elliot Hong, Robert Allen-Emerson, Robert P McMahon, Gunvant K Thaker.   

Abstract

BACKGROUND: Emerging data indicate the neuromodulator adenosine may play a role in the therapeutics of schizophrenia. Adenosine A(2A) receptor stimulation exerts a functional antagonism at postsynaptic D(2) receptors. Data from animal models relevant to schizophrenia support a therapeutic effect of modulating adenosinergic transmission in the ventral striatum. One previous clinical trial showed superiority of adjunctive dipyridamole, an adenosine reuptake inhibitor, compared to placebo in ameliorating positive symptoms in schizophrenia patients.
OBJECTIVES: The aim of this study was to examine the effects of dipyridamole monotherapy of 200 mg/day on positive and negative symptoms, with the goal of determining dosing for future adjunctive studies in schizophrenia.
METHODS: Twenty symptomatic schizophrenia participants were randomized to a 6-week double-blind trial comparing olanzapine (20 mg/day) to dipyridamole monotherapy (200 mg/day). Thirteen participants completed the treatment phase (eight on dipyridamole; five on olanzapine).
RESULTS: The olanzapine group showed a trend (p = 0.08) for superiority on BPRS total scores (mean ± SD: total BPRS score decreasing from 36.8 ± 2.3 at week 1, to 33.2 ± 5.5 at the end of the study). The mean total BPRS scores decreased from 36.4 ± 5.3 to 34.0 ± 7.7 in the dipyridamole group.
CONCLUSIONS: Although these pilot data do not support a significant antipsychotic effect of dipyridamole monotherapy, the results provide some evidence for examining dipyridamole (200 mg/day) as adjunct to symptomatic antipsychotic-treated schizophrenia patients.

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Year:  2011        PMID: 21537940      PMCID: PMC4009981          DOI: 10.1007/s00213-011-2315-3

Source DB:  PubMed          Journal:  Psychopharmacology (Berl)        ISSN: 0033-3158            Impact factor:   4.530


  36 in total

1.  Therapeutic benefit of adjunctive dipyridamole in schizophrenia is probably due to adenosine-glutamate interactions.

Authors:  M G Brunstein; P Belmonte-de-Abreu; D O Souza; D R Lara
Journal:  J Clin Pharm Ther       Date:  2001-04       Impact factor: 2.512

2.  The adenosine A1 receptor agonist N6-cyclopentyladenosine blocks the disruptive effect of phencyclidine on prepulse inhibition of the acoustic startle response in the rat.

Authors:  T L Sills; A Azampanah; P J Fletcher
Journal:  Eur J Pharmacol       Date:  1999-03-26       Impact factor: 4.432

3.  Selective adenosine A2A receptor/dopamine D2 receptor interactions in animal models of schizophrenia.

Authors:  S H Kafka; R Corbett
Journal:  Eur J Pharmacol       Date:  1996-01-11       Impact factor: 4.432

4.  Allopurinol augmentation for poorly responsive schizophrenia.

Authors:  D R Lara; M G Brunstein; E S Ghisolfi; M I Lobato; P Belmonte-de-Abreu; D O Souza
Journal:  Int Clin Psychopharmacol       Date:  2001-07       Impact factor: 1.659

5.  Dipyridamole in the treatment of schizophrenia: adenosine-dopamine receptor interactions.

Authors:  S Akhondzadeh; E Shasavand; H Jamilian; O Shabestari; A Kamalipour
Journal:  J Clin Pharm Ther       Date:  2000-04       Impact factor: 2.512

Review 6.  Adenosine A2A receptor antagonists for Parkinson's disease: rationale, therapeutic potential and clinical experience.

Authors:  Robert A Hauser; Michael A Schwarzschild
Journal:  Drugs Aging       Date:  2005       Impact factor: 3.923

7.  Beneficial antipsychotic effects of allopurinol as add-on therapy for schizophrenia: a double blind, randomized and placebo controlled trial.

Authors:  Shahin Akhondzadeh; Anosheh Safarcherati; Homayoun Amini
Journal:  Prog Neuropsychopharmacol Biol Psychiatry       Date:  2004-12-28       Impact factor: 5.067

Review 8.  Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic implications.

Authors:  Diogo R Lara; Oscar P Dall'Igna; Eduardo S Ghisolfi; Miriam G Brunstein
Journal:  Prog Neuropsychopharmacol Biol Psychiatry       Date:  2006-03-06       Impact factor: 5.067

9.  Dipyridamole attenuates the development of iminodipropionitrile-induced dyskinetic abnormalities in rats.

Authors:  M Tariq; S al-Deeb; K al-Moutaery; G W Bruyn; D A Evans; M Arshaduddin
Journal:  Brain Res Bull       Date:  1995       Impact factor: 4.077

10.  The effects of galantamine on psychopathology in chronic stable schizophrenia.

Authors:  Robert R Conley; Douglas L Boggs; Deanna L Kelly; Robert P McMahon; Dwight Dickinson; Stephanie Feldman; M Patricia Ball; Robert W Buchanan
Journal:  Clin Neuropharmacol       Date:  2009 Mar-Apr       Impact factor: 1.592

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  4 in total

Review 1.  Purinergic system in psychiatric diseases.

Authors:  A Cheffer; A R G Castillo; J Corrêa-Velloso; M C B Gonçalves; Y Naaldijk; I C Nascimento; G Burnstock; H Ulrich
Journal:  Mol Psychiatry       Date:  2017-09-26       Impact factor: 15.992

2.  Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the "adenosine hypothesis".

Authors:  Elisabet Aliagas; Izaskun Villar-Menéndez; Jean Sévigny; Mercedes Roca; Miriam Romeu; Isidre Ferrer; Mireia Martín-Satué; Marta Barrachina
Journal:  Purinergic Signal       Date:  2013-06-16       Impact factor: 3.765

3.  Repurposing Dipyridamole in Niemann Pick Type C Disease: A Proof of Concept Study.

Authors:  Rita Pepponi; Roberta De Simone; Chiara De Nuccio; Sergio Visentin; Andrea Matteucci; Antonietta Bernardo; Patrizia Popoli; Antonella Ferrante
Journal:  Int J Mol Sci       Date:  2022-03-22       Impact factor: 5.923

Review 4.  Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?

Authors:  Abdul-Rizaq Hamoud; Karen Bach; Ojal Kakrecha; Nicholas Henkel; Xiaojun Wu; Robert E McCullumsmith; Sinead M O'Donovan
Journal:  Int J Mol Sci       Date:  2022-10-05       Impact factor: 6.208

  4 in total

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