Chloroquine-induced scratching is mediated by NO/cGMP pathway in mice.

Chloroquine (CQ), a 4-aminoquinoline drug, has long been used in the treatment and prevention of malaria. However its side effect generalized pruritus contributes to treatment failures, and consequently results in the development of chloroquine resistant strains of Plasmodium falciparum. It was proposed that the administration of CQ correlated with increase in nitric oxide (NO) production. Nitric oxide is involved in some pruritic disorders such as atopic dermatitis, psoriasis and scratching behavior evoked by pruritogens like substance P. Therefore, the aim of this study was to investigate the involvement of NO/cGMP pathway in CQ-induced scratching in mice. Scratching behaviors were recorded by a camera after intradermal (ID) injection of CQ in the shaved rostral back of the mice. The results obtained show that CQ elicited scratching in a dose-dependent manner with a peak effective dose of 400µg/site. Injection of non-specific NOS inhibitor, N-nitro-l-arginine methyl ester or neuronal NOS selective inhibitor and 7-nitroindazole, reduced CQ-induced scratching significantly. On the other hand, administration of aminoguanidine as inducible NOS inhibitor has no inhibitory effect on this behavior. Also, injection of l-arginine as a precursor of NO significantly increased this response. Conversely, accumulation of cGMP by sildenafil as a selective phosphodiesterase type 5 inhibitor, potentiated the scratching behavior by CQ. This study therefore shows that CQ-induced scratching behavior is mediated by the NO/cGMP pathway.

Teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses.

Objective. Depression during pregnancy is a relatively common problem. Since little is known about the teratogenic effects of concomitant administration of fluoxetine and olanzapine during the organogenesis period, the aim of the present study was to evaluate the teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses. Method. Forty-two pregnant rats were divided into seven groups, randomly. The first group received 0.5 mL of normal saline as the control. The second and third groups received fluoxetine at doses of 9 mg/kg and 18 mg/kg, respectively. Olanzapine was injected at 3 mg/kg and 6 mg/kg to the fourth and fifth groups, respectively. The sixth group received 9 mg/kg fluoxetine and 3 mg/kg olanzapine. Finally, the seventh group was administrated with fluoxetine and olanzapine at 18 mg/kg and 6 mg/kg, respectively. Drugs were injected intraperitoneally between day eight and day 15 of the pregnancy. On the 17th day of pregnancy, the fetuses were removed and micro-/macroscopically studied. Results. Fetuses of rats receiving high doses of these drugs showed a significant rate of cleft palate development, premature eyelid opening and torsion anomalies, compared to the control group (P ≤ 0.01). It is concluded that these drugs can lead to teratogenicity, so their concomitant use during pregnancy should be avoided, or if necessary their doses must be decreased.