The influence of psychotropic drugs on the phosphodiesterase activity in the rat brain meninges.
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.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004388:Dura Mater / Q000201:enzymology*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010841:Pia Mater / Q000201:enzymology*; D051381:Rats; D013346:Subarachnoid Space / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D010640:Phenothiazines; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases