Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2.

The neuronal vesicular monoamine transporter (VMAT2) is the target molecule of action of some psychostimulants, such as methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The present study examined the effect of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), on VMAT2 activity by measuring adenosine triphosphate-dependent [(3)H]dopamine uptake into synaptic vesicles prepared from rat striatum. SSRIs, fluoxetine, paroxetine, and fluvoxamine, inhibited vesicular [(3)H]dopamine uptake in vitro. The rank order of potency was reserpine>>fluoxetine, paroxetine>fluvoxamine, methamphetamine>MDMA. Moreover, kinetic analysis revealed that inhibition by reserpine, a typical VMAT2 inhibitor, was uncompetitive, decreasing maximum velocity and affinity for dopamine. Inhibition by fluoxetine was noncompetitive, only decreasing maximum velocity for dopamine. These results suggest that fluoxetine inhibited the activity of VMAT2 by a mechanism different from that of reserpine and did not directly interact with the active site of VMAT2.

[Concentrations of sevoflurane with and without nitrous oxide to block vasomotor reflexes to incision (MACBVR)].

The minimum alveolar concentration of an anesthetic that blocks the skin vasomotor reflex to surgical incision (MACBVR) for sevoflurane was determined in 37 patients aged 30-60 years scheduled for laparotomies with or without nitrous oxide. Thirty seven patients were randomly allocated to one of the two groups: a sevoflurane group and a sevoflurane/N2O (50 vol%) group. The skin blood flow of the finger tip was measured using a laser Doppler flowmeter. Anesthesia was induced with sevoflurane and N2O and tracheal intubation was facilitated with vecuronium 0.1 mg.kg-1. Predetermined end tidal concentrations of sevoflurane and N2O were maintained for at least 15 min before incision. The MACBVR values of sevoflurane in O2 and in the presence of 50% N2O were 3.07% and 1.63%, respectively. The MACBVR level in the total anesthetic MAC multiple was 1.75 MAC for sevoflurane alone and the value decreased to 1.43 MAC when 50% N2O was used. There were no relations between the amplitude of the reduction in skin blood flow and the changes of hemodynamic variables in each group. However, the changes in SBP and HR at incision were significantly suppressed by addition of N2O (changes in SBP and HR: 41.6 +/- 20.4 mmHg and 35.4 +/- 12.5 bpm in the sevoflurane group vs. 24.6 +/- 10.2 mmHg and 18.1 +/- 9.5 bpm in the sevoflurane/N2O group, P < 0.01). The results suggest that N2O is useful to suppress adrenergic responses to a surgical stimulus during sevoflurane anesthesia.