Effects of carbamazepine on dopamine function in rodents.
Carbamazepine (CBZ), a drug with acute antimanic and prophylactic activity in the treatment of manic depressive psychosis, was administered to rats in their diet, resulting in plasma levels of 5-10 micrograms/ml, which is within the human therapeutic range. Chronic CBZ (14 days) did not increase hyperactivity stimulated by the dopamine agonist apomorphine (1.0 mg/kg or 0.5 mg/kg), or to methylamphetamine (0.75 mg/kg), a dopamine releasing agent. Chronic CBZ failed to attenuate the development of enhanced sensitivity to methylamphetamine (0.75 mg/kg) produced by chronic haloperidol (2 mg/kg daily), in contrast to the known attenuation produced by lithium. Pretreatment with CBZ attenuated the hypoactivity produced by apomorphine (0.08 mg/kg), suggesting possible decreased sensitivity of presynaptic dopamine auto-receptors inhibiting dopamine release. Pretreatment with CBZ for 14 days decreased accumulation of L-dopa after administration of NSD 1015 (100 mg/kg IP), an amino acid decarboxylase inhibitor, in the frontal cortex, suggesting decreased dopamine synthesis. These findings suggest that the anti-manic activity of CBZ is neither related to a dopamine blocking action similar to that of neuroleptics, or to an attenuation of dopamine regulatory mechanisms similar to that of lithium. However, chronic CBZ may have some effects on presynaptic dopamine function, indicated by reduced sensitivity of presynaptic dopamine receptors, which may be related to its therapeutic action.
Elphick
M
M
University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors
D011954:Receptors, Dopamine; D002220:Carbamazepine; D008694:Methamphetamine; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine