Serotonin syndrome: a concise review of a toxic state.

The serotonin syndrome is a toxic state caused by increased intrasynaptic serotonin and characterized by a triad of altered mental status, autonomic instability and neuromuscular abnormalities. It can result from exposure to a single serotonergic agent but is more likely to be due to polypharmacy, often with drugs from multiple classes. It develops over a short period of time and resolves just as quickly once identified and treated. Diagnostic criteria have been developed to assist in clinical practice. Treatment is largely supportive and prognosis is generally very favorable. Pharmacologic vigilance and prevention are key.

Changes in caudate volume after exposure to atypical neuroleptics in patients with schizophrenia may be sex-dependent.

BACKGROUND: Changes in the volume of the caudate nucleus over time in patients with schizophrenia has been shown to be directly related to neuroleptic exposure. Few studies have evaluated caudate volume in subjects with schizophrenia who were neuroleptic naive at intake and treated exclusively with atypical neuroleptics. METHODS: Fourteen patients were matched by gender to 14 healthy controls and were evaluated over time using MRI. The patients were neuroleptic naïve at intake and at follow-up had been treated exclusively with atypical neuroleptics. Difference scores were calculated for caudate volumes. Neuroleptic exposure was quantified using a dose-years formula. RESULTS: There was no difference between patients and controls in the amount of change over time in the volume of the caudate. However, the female patients had a negative correlation (r= - 0.74) between drug exposure and volume change while the male patients had a positive correlation (r = 0.63). Therefore, there was a significant gender effect on the relationship between atypical neuroleptic exposure and changes in the structure of the caudate over time (test for difference in correlations: z = 2.39, p = 0.016). CONCLUSIONS: The change in caudate nucleus volume over time with exposure to atypical neuroleptics may be sex-dependent. Atypical neuroleptic expsoure was associated with volume increase over time in the males, while exposure in females was associated with volume decrement over time.

Cannabinoids attenuate capsaicin-evoked hyperalgesia through spinal and peripheral mechanisms.

Previous studies in our laboratory have demonstrated that cannabinoids administered intravenously attenuate the duration of nocifensive behavior and block the development of hyperalgesia produced by intraplantar injection of capsaicin. In the present study, we extended these observations and determined whether cannabinoids attenuate capsaicin-evoked pain and hyperalgesia through spinal and peripheral mechanisms, and whether the antihyperalgesia was receptor mediated. Separate groups of rats were pretreated 7 min before capsaicin with an intrathecal injection of vehicle or the cannabinoid receptor agonist WIN 55,212-2 at doses of 0.1, 1.0 or 10 microg in 10 microl. Although the intrathecal application of WIN 55,212-2 did not alter nocifensive behavior following capsaicin, it produced a dose-dependent decrease in hyperalgesia to heat and mechanical stimuli. Intrathecal pretreatment with the CB1 receptor antagonist SR141716A (10 microg) blocked the antihyperalgesia produced by WIN 55,212-2. The ability of intrathecal administration of WIN 55,212-2 to attenuate hyperalgesia was not due to motor deficits since the highest dose of WIN 55,212-2 did not alter performance on the rota-rod test. To investigate whether cannabinoids attenuated capsaicin-evoked hyperalgesia through peripheral mechanisms, separate groups of rats were pretreated with an intraplantar injection of WIN 55,212-2 at doses of 0.1, 1.0, 10 or 30 microg in 100 microl 5 min before capsaicin. Intraplantar pretreatment with WIN 55,212-2 produced a dose-dependent attenuation of hyperalgesia to heat, but did not attenuate mechanical hyperalgesia or the duration of nocifensive behavior. The inactive enantiomer WIN 55,212-3 did not alter the development of hyperalgesia. SR141716A (100 microg) co-injected with WIN 55,212-2 (30 microg) partially attenuated the effects of WIN 55,212-2 on hyperalgesia to heat. Intraplantar injection of the highest dose of WIN 55,212-2 did not interfere with the development of hyperalgesia following capsaicin injection into the contralateral paw. These data show that cannabinoids possess antihyperalgesic properties at doses that alone do not produce antinociception, and are capable of acting at both spinal and peripheral sites.