A series of bupropion (1a) analogues (1b-1ff) were synthesized, and their in vitro and in vivo pharmacological properties evaluated with the goal of developing a 1a analogue that had better properties for treating addictions. Their in vitro pharmacological properties were examined by [(3)H]dopamine ([(3)H]DA), [(3)H]serotonin ([(3)H]5HT), and [(3)H]norepinephrine ([(3)H]NE) uptake inhibition studies, and by binding studies at the dopamine, serotonin, and norepinephrine transporters using [(125)I]RTI-55 in cloned transporters. Several analogues showed increased [(3)H]DA uptake inhibition with reduced or little change in [(3)H]5HT and [(3)H]NE uptake inhibition relative to bupropion. Thirty-five analogues were evaluated in a 1 h locomotor activity observation test and 32 in an 8 h locomotor activity observation test and compared to the locomotor activity of cocaine. Twenty-four analogues were evaluated for generalization to cocaine drug discrimination after i.p. administration, and twelve analogues were tested in a time course cocaine discrimination study using oral administration. 2-(N-Cyclopropylamino)-3-chloropropiophenone (1x) had the most favorable in vitro efficacy and in vivo pharmacological profile for an indirect dopamine agonist pharmacotherapy for treating cocaine, methamphetamine, nicotine, and other drugs of abuse addiction.

Bupropion (2a) analogues were synthesized and tested for their ability to inhibit monoamine uptake and to antagonize the effects of human α3β4*, α4β2, α4β4, and α1* nAChRs. The analogues were evaluated for their ability to block nicotine-induced effects in four tests in mice. Nine analogues showed increased monoamine uptake inhibition. Similar to 2a all but one analogue show inhibition of nAChR function selective for human α3β4*-nAChR. Nine analogues have higher affinity at α3β4*-nAChRs than 2a. Four analogues also had higher affinity for α4β2 nAChR. Analogues 2r, 2m, and 2n with AD 50 values of 0.014, 0.015, and 0.028 mg/kg were 87, 81, and 43 times more potent than 2a in blocking nicotine-induced antinociception in the tail-flick test. Analogue 2x with IC 50 values of 31 and 180 nM for DA and NE, respectively, and IC 50 = 0.62 and 9.8 μm for antagonism of α3β4 and α4β2 nAChRs had the best overall in vitro profile relative to 2a.

BackgroundConfusion about how to assess for intolerance to feedings often results in unnecessary feeding interruptions.ObjectivesTo report findings from a national survey of methods used by critical care nurses to assess tolerance to gastric tube feedings and to discuss the findings in light of current enteral nutrition guidelines.MethodsA paper-and-pencil survey was mailed to 1909 members of the American Association of Critical-Care Nurses. In addition, the same survey was posted online in a newsletter circulated to association members. Results from both surveys were pooled for data analysis.ResultsA total of 2298 responses were obtained; most respondents reported using a combination of methods to assess tolerance to gastric tube feedings (listening for bowel sounds, measuring gastric residual volumes, observing for abdominal distention/discomfort and for nausea and vomiting). More than 97% of the nurses reported measuring gastric residual volumes; the most frequently cited threshold levels for interrupting feedings were 200 mL and 250 mL. About 25% of the nurses reported interrupting feedings for gastric residual volumes of 150 mL or less; only 12.6% of the respondents reported allowing gastric residual volumes of up to 500 mL before interrupting feedings.ConclusionsPractice among the 2298 critical care nurses varied widely. Many of the survey respondents are practicing in ways that can unnecessarily diminish the delivery of calories to patients. Protocols based on current enteral nutrition guidelines must be developed and implemented in practice settings.

Freundlich adsorption isotherms were obtained for gamma‐ and beta‐isomers of 1,2,3,4,5,6‐hexachlorocyclohexane adsorbed from aqueous and hexane solvents on Ca‐Staten peaty muck, Ca‐bentonite Ca‐Venado clay, and silica gel in the temperature range of 10 to 40C. Comparison of normal and “corrected” isotherms revealed a significant effect on adsorption due to the influence of temperature on solubility. The 1/n constants of the Freundlich equation increased with temperature according to the theory of dilute solutions. When the solubility effect is removed, the gamma isomer has greater adsorbability than the beta isomer, possibly because the former possesses a dipole moment whereas the latter does not. At constant solution fugacities, the gamma isomer on Staten peaty muck competed somewhat more effectively with hexane than with water.