Effects of phosphodiesterase 10 inhibition on striatal cyclic AMP and peripheral physiology in rats

• Autorzy: Torremans A. , Ahnaou A. , Van Hemelrijck A. , Straetemans R. , Geys H. , Vanhoof G. , Meert T. F. , Drinkenburg W. H.
• Języki publikacji: EN

Abstrakty

EN

Phosphodiesterases (PDEs) form a family of enzymes involved in the hydrolysis of cyclic adenosine and guanosine monophosphate (cAMP and cGMP). PDE10A is a member of this family that is almost exclusively expressed in the striatum. Increasing cAMP/cGMP levels via inhibition of PDE10A is under consideration as a novel therapeutic avenue in the discovery of antipsychotics. Papaverine has been used as a pharmacological tool to establish the possible clinical use of PDE10A inhibitors as antipsychotics. Papaverine is known to increase cAMP levels in striatum and to decrease blood pressure, body temperature and locomotor activity after systemic administration. In this study, the effects of papaverine are compared to those of a more specific PDE10A inhibitor MP10. Papaverine raised striatal cAMP levels with hypothermia, hypoactivity and decreased cardiovascular responses. The more selective MP10 had significantly less effects on body temperature and cardiovascular functions, but reduced locomotor activity to a similar extend as papaverine.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2010
• Tom: 70
• Numer: 1
• Opis fizyczny: p.13-19,fig.,ref.

Twórcy

autor

Torremans A.

• Johnson and Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

autor

Ahnaou A.

• Johnson and Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

autor

Van Hemelrijck A.

• Johnson and Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

autor

Straetemans R.

• Johnson and Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

autor

Geys H.

• Johnson and Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

autor

Vanhoof G.

• Johnson and Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

autor

Meert T. F.

• Johnson and Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

autor

Drinkenburg W. H.

• Johnson and Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

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