Antipsychotic drugs represent the most effective treatment for chronic
psychotic disorders. The newer second generation drugs offer the advantage of fewer neurological side-effects compared to prior drugs, but many cause serious metabolic side-effects. The underlying physiology of these side-effects is not well-understood, but evidence exists to indicate that the sympathetic nervous system may play an important role. In order to examine this possibility further, we treated separate groups of adult female rats acutely with either the first generation
antipsychotic drug haloperidol (0.1 or 1 mg/kg) or the second generation drugs
risperidone (0.25 or 2.5 mg/kg),
clozapine (2 or 20 mg/kg),
olanzapine (3 or 15 mg/kg) or vehicle by
intraperitoneal injection. Blood samples were collected prior to
drug and then 30, 60, 120, and 180 mins
after treatment. Plasma samples were assayed by HPLC-ED for levels of
norepinephrine,
epinephrine, and
dopamine. Results confirmed that all
antipsychotics increased peripheral
catecholamines, although this was
drug and dose dependent. For
norepinephrine,
haloperidol caused the smallest maximum increase (+158%], followed by
risperidone (+793%),
olanzapine (+952%) and
clozapine (+1,684%). A similar pattern was observed for increases in
epinephrine levels by
haloperidol (+143%],
olanzapine (+529%),
risperidone (+617%) then
clozapine (+806%).
Dopamine levels increased moderately with
olanzapine [+174%],
risperidone [+271%], and
clozapine [+430%]. Interestingly, levels of the
catecholamines did not correlate strongly with each other prior to treatment at baseline, but were increasingly correlated
after treatment as time proceeded. The results demonstrate
antipsychotics can potently regulate peripheral
catecholamines, in a manner consistent with their metabolic liability.