Recurrent headaches may be caused by cerebral toxoplasmosis

Table 5 Drugs tested for in vitro activity against Toxoplasma gondii (according to Jones-Brando et al[52]; with own modification)

Drug	Solvent	ID501 (μg/mL)	TD502 (μg/mL)	TI3
Valproic acid	Ethanol	4.5	62.4	13.9
Sodium valproate	Ethanol	4.1	52	12.7
Carbamazepine	Ethanol	72	100	1.3
Lithium carbonate	1 N HCl	> 100	> 100
Haloperidol	Ethanol	5.6	103	18.4
9-OH-Risperidone	Tartaric acid	20.1	134	6.7
Risperidone	Tartaric acid	74	129	1.7
Fluphenazine HCl	Toxo CGM	3.5	17.9	5.1
Clozapine	Ethanol	5.8	20	3.4
Olanzapine	DMSO	33.2	100	3
Chlorpromazine HCl	DMSO	2.6	6	2.3
Quetiapine fumarate	DMSO	18.6	33	1.8
Trimethoprim	DMSO	5.3	63.8	12.1

¹Median inhibitory dose, a measure of tachyzoite inhibition.

²Median toxicity dose, a measure of cytotoxicity.

³Therapeutic index, a measure of efficacy determined by TD₅₀/ID₅₀ ratio. Valproic acid at a concentration of 1 μg/mL inhibited 7% of the tachyzoites and trimethoprim at 3.2 μg/mL produced 2% inhibition, but the combination of these two compounds at those concentrations resulted in a potentiating effect inhibiting 55% of the tachyzoites. Recently, Fond et al[53] also reported that other antipsychotic drugs, such as amisulpride, cyamemazine, levopromazine, loxapine, tiapride and zuclopenthixol in vitro exerted anti-toxoplasmatic activity in the range of 0.19 to 1 μmol/L concentrations. The inhibitory concentration 50 (IC₅₀) for the last preparation was 8 ± 1.8 μmol/L while its serum levels varied from 0.01-0.12 μmol/L[54], but antipsychotic drugs usually achieve much higher and persistent concentrations in the brain tissue[55]. In human fibroblast cell cultures, IC₅₀ for fluphenazine, thioridazine and trifluoperazine against developing tachyzoites of the parasite RH strain was 1.7, 1.2 and 3.8 μmol/L, respectively[56]. DMSO: Dimethylsulfoxide; Toxo CGM: Toxoplasma cell growth medium; TI: Therapeutic index; TD: Median toxicity dose; ID: Median inhibitory dose.