The influence of psychotropic drugs on the phosphodiesterase activity in the rat brain meninges.

ABSTRACT

Phosphodiesterase (PDE) is present in brain meninges. Its activity is higher in the pia than in the dura mater. Phenothiazine neuroleptics fluphenazine, trifluoroperazine, thioproperazine, chloropromazine and thioridazine at concentration 10(-5)--10(-4) M in vitro inhibit the PDE activity in the pia and dura mater. Most potent in this respect were fluphenazine and trifluoroperazine. Much less pronounced inhibition of PDE activity in brain meninges was found after in vitro administration of tricyclic antidepressant nortriptyline, chlorimipramine, protriptyline, desipramine and imipramine in concentrations 10(-4)--10(-3) M. Administered in vivo in a dose of 0.1 mg or 5 mg/kg ip fluphenazine inhibited the hydrolysis of 32P-cAMP injected into subarachnoid space. The results indicate that PDE present in the rat brain meninges may control the cAMP level in the cerebrospinal fluid. Treatment with phenothiazine neuroleptics which inhibit the PDE activity in meninges may significantly depress the hydrolysis of cAMP in the cerebrospinal fluid.