Synthesis, F-18 radiolabeling, and microPET evaluation of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines as ligands of the corticotropin-releasing factor type-1 (CRF1) receptor.

A series of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines were synthesized and evaluated as potential positron emission tomography (PET) tracers for the corticotropin-releasing factor type-1 (CRF1) receptor. Compounds 27, 28, 29, and 30 all displayed high binding affinity (⩽1.2 nM) to the CRF1 receptor when assessed by in vitro competition binding assays at 23 °C, whereas a decrease in affinity (⩾10-fold) was observed with compound 26. The logP7.4 values of [(18)F]26-[(18)F]29 were in the range of ∼2.2-2.8 and microPET evaluation of [(18)F]26-[(18)F]29 in an anesthetized male cynomolgus monkey demonstrated brain penetrance, but specific binding was not sufficient enough to differentiate regions of high CRF1 receptor density from regions of low CRF1 receptor density. Radioactivity uptake in the skull, and sphenoid bone and/or sphenoid sinus during studies with [(18)F]28, [(18)F]28-d8, and [(18)F]29 was attributed to a combination of [(18)F]fluoride generated by metabolic defluorination of the radiotracer and binding of intact radiotracer to CRF1 receptors expressed on mast cells in the bone marrow. Uptake of [(18)F]26 and [(18)F]27 in the skull and sphenoid region was rapid but then steadily washed out which suggests that this behavior was the result of binding to CRF1 receptors expressed on mast cells in the bone marrow with no contribution from [(18)F]fluoride.

Feasibility and analgesic efficacy of the transversus abdominis plane block after single-port laparoscopy in patients having bariatric surgery.

PURPOSE: The transversus abdominis plane (TAP) block is a technique increasingly used for analgesia after surgery on the anterior abdominal wall. We undertook this study to determine the feasibility and analgesic efficacy of ultrasound-guided TAP blocks in morbidly obese patients. We describe the dermatomal spread of local anesthetic in TAP blocks administered, and test the hypothesis that TAP blocks decrease visual analog scale (VAS) scores. PATIENTS AND METHODS: After ethics committee approval and informed consent, 35 patients with body mass index >35 undergoing single-port sleeve gastrectomy (SPSG) were enrolled. All patients received balanced general anesthesia, followed by intravenous patient-controlled analgesia (IV-PCA; hydromorphone) postoperatively; all reported VAS >3 upon arrival to the recovery room. From the cohort of 35 patients having single-port laparoscopy (SPL), a sealed envelope method was used to randomly select ten patients to the TAP group and 25 patients to the control group. The ten patients in the TAP group received ultrasound-guided TAP blocks with 30 mL of 0.2% Ropivacaine injected bilaterally. The dermatomal distribution of the sensory block (by pinprick test) was recorded. VAS scores for the first 24 hours after surgery and opioid use were compared between the IV-PCA+TAP block and IV-PCA only groups. RESULTS: Sensory block ranged from T5-L1. Mean VAS pain scores decreased from 8 ± 2 to 4 ± 3 (P=0.04) within 30 minutes of TAP block administration. Compared with patients given IV-PCA only, significantly fewer patients who received TAP block had moderate or severe pain (VAS 4-10) after block administration at 6 hours and 12 hours post-surgery. However, cumulative consumption of hydromorphone at 24 hours after SPSG surgery was similar for both groups. CONCLUSION: Ultrasound-guided TAP blocks in morbidly obese patients are feasible and result in satisfactory analgesia following SPSG in the immediate postoperative period.