Novel quinazolinone derivatives as 5-HT7 receptor ligands.

5-HT(7) receptor antagonists generated antidepressant-like effects in animal model and the involvement of the 5-HT(7) receptor in other pathophysiological mechanisms such as thermoregulation, learning and memory, and sleep has been highlighted by various studies. As one of our efforts to discover a new type of 5-HT(7) receptor antagonists, we here report on the synthesis and binding affinities to the 5-HT(7) receptor of the quinazolinone library 1, which was designed with various substituents (X, Y, R(1), and R(2)) on the aromatic rings and different carbon chain length. Total 85 compounds of the quinazolinone library 1 were synthesized and the binding affinities of all the synthesized compounds were obtained by radioligand binding assay for the 5-HT(7) receptor. Among the 85 compounds, 24 compounds show very good binding affinities with IC(50) values below 100 nM. Mainly the compounds with IC(50) values below 100 nM have o-OMe or o-OEt as R(2) substituent. The compound with the best binding affinity is 1-68 of which the IC(50) value is 12 nM. In in vivo animal study, some synthesized compounds really have the antidepressant activity in the forced swimming test in mice.

Comparison of clinical effects according to the dosage of sufentanil added to 0.5% hyperbaric bupivacaine for spinal anesthesia in patients undergoing cesarean section.

BACKGROUND: Subarachnoid block is a widely used technique for cesarean section. To improve the quality of analgesia and prolong the duration of analgesia, addition of intrathecal opioids to local anesthetics has been encouraged. We compared the effects of sufentanil 2.5 µg and 5 µg, which were added to intrathecal hyperbaric bupivacaine. METHODS: We enrolled 105 full term parturients were randomly divided into 3 groups: Group 1 (control), Group 2 (sufentanil 2.5 µg), and Group 3 (sufentanil 5 µg). In every group, 0.5% heavy bupivacaine was added according to the adjusted dose regimen. We determined the maximum level of sensory block and motor block, the quality of intraoperative analgesia, the duration of effective analgesia and side effects. RESULTS: There were no significant differences among the 3 groups in the maximum level of the sensory block and motor block. Recovery rate of the sensory block, however, was significantly slower in Group 3 than Group 1. Quality of intraopertive analgesia, muscle relaxation, and duration of effective analgesia were enhanced by increasing the dosage of intrathecal sufentanil. Frequencies of hypotension, maximum sedation level, and pruritus were directly related to the dosage of intrathecal sufentanil, whereas nausea and vomiting occurred only in the groups using sufentanil. CONCLUSIONS: The addition of sufentanil 2.5 µg for spinal anesthesia provides adequate intraoperative analgesia and good postoperative analgesia with minimal adverse effects on the mother.

Comparison of fentanyl and sufentanil added to 0.5% hyperbaric bupivacaine for spinal anesthesia in patients undergoing cesarean section.

BACKGROUND: Subarachnoid block is widely used for cesarean section due to the rapid induction, the complete analgesia, the low failure rate and the prevention of aspiration pneumonia. The addition of intrathecal opioids to local anesthetics seems to improve the quality of analgesia & prolong the duration of analgesia. Therefore we compared the effects of fentanyl 20 µg and sufentanil 2.5 µg, which were added to intrathecal hyperbaric bupivacaine. METHODS: SEVENTY TWO HEALTHY TERM PARTURIENTS WERE RANDOMLY DIVIDED INTO THREE GROUPS: Group C (control), Group F (fentanyl 20 µg) and Group S (sufentanil 2.5 µg). In every group, 0.5% heavy bupivacaine was added according to the adjusted dose regimen by Harten et al. We observed the maximal level of the sensory block and motor block, the quality of intraoperative analgesia, the duration of effective analgesia and the side effects. RESULTS: There were significant differences between the control and the fentanyl 20 µg and sufentanil 2.5 µg groups for the degree of muscle relaxation, the quality of intraoperative analgesia, the maximal sedation level and the duration of effective analgesia. The frequencies of side effects such as nausea and pruritis in the opioid groups were higher than those in the control group. But there were no differences between fentanyl 20 µg and sufentanil 2.5 µg for the frequencies of nausea and pruritis. CONCLUSIONS: The addition of fentanyl 20 µg or sufentanil 2.5 µg for spinal anesthesia provides adequate intraoperative analgesia without significant adverse effects on the mother and neonate.

Anesthetic management for emergent Cesarean section in a patient with toxic epidermal necrolysis -A case report-.

Toxic epidermal necrolysis (TEN) is rare but serious cutaneous reaction with significant mortality and long-term morbidity. Various etiologies, particularly numerous medications and infectious agents have been implicated. It is characterized as inflammatory bullous lesions of the skin and mucous membrane and can develop serious complications such as pneumonia, pneumothorax, sepsis and renal failure. In general, patients with TEN are managed as severe second-degree burn patients with preventing excessive fluid deficit and infections. In this case, we aimed to present anesthetic management of a 26-year-old pregnant woman with TEN who received general anesthesia during emergent cesarean section.

Amniotic fluid embolism that took place during an emergent Cesarean section -A case report-.

Amniotic fluid embolism (AFE) is a rare but fatal obstetric emergency, characterized by sudden cardiovascular collapse, dyspnea or respiratory arrest and altered mentality, disseminated intravascular coagulation (DIC). It can lead to severe maternal morbidity and mortality, but the prediction of its occurrence and treatment are very difficult. We experienced a case of AFE during emergent Cesarean section in a 40(+6) weeks healthy pregnant woman, age 33. Sudden dyspnea, hypotension, signs of pulmonary edema and DIC were developed during Cesarean section, and cardiac arrest followed after these events. The course of these events was so rapid and catastrophic, which was consistent with AFE. Thus, we report this case precisely and review pathophysiology, diagnosis, treatment of AFE by referring to up-to-date literatures.

A case of displaced pulmonary artery catheter into hepatic vein in mitral insufficiency patient: A case report.

A 47-year-old woman was scheduled for mitral valvoplasty. Before induction of anesthesia, a pulmonary artery catheter (PAC) was placed via right internal jugular vein. Central venous pressure or right atrial pressure was traced until about 60 cm of PAC insertion and right ventricular pressure curve appeared without arrhythmias. We withdrew and advanced the catheter several times, but pressure tracing showed the same pattern. And we could not obtain the pulmonary artery pressure. We decided to leave the PAC in the right ventricle. No ventricular arrhythmia was detected. Postoperative chest x-ray revealed that PAC traveled through inferior vena cava and looped in the hepatic vein with the tip of the catheter in the right ventricle. Under fluoroscopic guidance, PAC was inserted to the pulmonary artery. No sign of hepatic vein obstruction was detected.