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A new series of cysLT1 receptor antagonists represented by CP-288,886 (7) and CP-265,298 (8) were developed which are equipotent to clinical cysLT1 receptor antagonists Zafirlukast (1) and Pranlukast (2).

We report the first neutron triple-differential cross-sections measured in multiplicity-selected heavy-ion collisions. We examine the maximum azimuthal anisotropy ratio of these neutron cross-sections from 400 AMeV Nb-Nb and Au-Au collisions as a probe of the nuclear equation of state. Experiment reveals that this ratio does not depend on the mass of the colliding nuclei, contrary to the predictions of the Quantum Molecular Dynamics (QMD) transport theory. We compare the Nb-Nb data also with theoretical calculations done within the Boltzmann-Uehling-Uhlenbeck framework with both momentum-dependent and momentum-independent interactions. We find that the experiment is sensitive to the size of the nuclear incompressibility modulus K in the nuclear matter equation of state, and that the data demand a K value compatible with state-of-the-art nuclear matter calculations.

Neutron yields and energy spectra were measured for 35 MeV deuterons on a thick target of natural lithium. Data were obtained using the time-of-flight technique over an angular range of 0° to 150° and for neutron energies from about 1 to 50 MeV. A simple nuclear model that describes the differential cross sections of neutron production was adjusted to agree with these new thick target data. Different model parameters were obtained when the model was adjusted to agree with previous ORNL thick target data for 40 MeV deuterons. Our experimental data are in good agreement with model predictions based upon the ORNL time-of-flight data but are somewhat lower than predictions based upon the ORNL dosimetry data. Finally the model was used to predict the neutron spectrum at the position of highest flux in the FMIT test cell.

1The selective NK1receptor antagonist, CP‐99,994, produced dose‐related (0.1‐1.0 mg kg−1, s.c.) inhibition of vomiting and retching in ferrets challenged with central (loperamide and apomorphine), peripheral (CuSO4) and mixed central and peripheral (ipecac, cisplatin) emetic stimuli.2Parallel studies with the enantiomer, CP‐100,263 (1 mgkg−1, s.c), which is > 1 000 fold less potent as a NK1antagonist, indicated that it was without significant effect against CuSO4, loperamide, cisplatin and apomorphine‐induced emesis. Against ipecac, it inhibited both retching and vomiting, expressing approximately l/10th the potency of CP‐99,994.3The 5‐HT3receptor antagonist, tropisetron (lmgkg−1, s.c.) inhibited retching and vomiting to cisplatin and ipecac, but not CuSO4or loperamide.4CP‐99,994 (lmgkg−1, i.v.) blocked retching induced by electrical stimulation of the ventral abdominal vagus without affecting the cardiovascular response, the apnoeic response to central vagal stimulation or the guarding and hypertensive response to stimulation of the greater splanchnic nerves. CP‐99,994 (1 mg kg−1, i.v.) did not alter baseline cardiovascular and respiratory parameters and it failed to block the characteristic heart rate, blood pressure and respiratory rate/depth changes in response to i.v. 2‐methyl‐5‐HT challenge (von Bezold‐Jarisch reflex).5Using in vitroautoradiography, [3H]‐substance P was shown to bind to several regions of the ferret brainstem with the density of binding in the nucleus tractus solitarius being much greater than in the area postrema. This binding was displaced by CP‐99,994 in a concentration‐related manner.6In dogs, CP‐99,994 (40 μg kg−1bolus and 300 μg kg−1h−1, i.v.) produced statistically significant reductions in vomiting to CuSO4and apomorphine as well as retching to CuSO4.7Together, these studies support the hypothesis that the NK1receptor antagonist properties of CP‐99,994 are responsible for its broad spectrum anti‐emetic effects. They also suggest that CP‐99,994 acts within the brainstem, most probably within the nucleus tractus solitarius although the involvement of the area postrema could not be excluded. The selective NK1receptor antagonist, CP‐99,994, produced dose‐related (0.1‐1.0 mg kg−1, s.c.) inhibition of vomiting and retching in ferrets challenged with central (loperamide and apomorphine), peripheral (CuSO4) and mixed central and peripheral (ipecac, cisplatin) emetic stimuli. Parallel studies with the enantiomer, CP‐100,263 (1 mgkg−1, s.c), which is > 1 000 fold less potent as a NK1antagonist, indicated that it was without significant effect against CuSO4, loperamide, cisplatin and apomorphine‐induced emesis. Against ipecac, it inhibited both retching and vomiting, expressing approximately l/10th the potency of CP‐99,994. The 5‐HT3receptor antagonist, tropisetron (lmgkg−1, s.c.) inhibited retching and vomiting to cisplatin and ipecac, but not CuSO4or loperamide. CP‐99,994 (lmgkg−1, i.v.) blocked retching induced by electrical stimulation of the ventral abdominal vagus without affecting the cardiovascular response, the apnoeic response to central vagal stimulation or the guarding and hypertensive response to stimulation of the greater splanchnic nerves. CP‐99,994 (1 mg kg−1, i.v.) did not alter baseline cardiovascular and respiratory parameters and it failed to block the characteristic heart rate, blood pressure and respiratory rate/depth changes in response to i.v. 2‐methyl‐5‐HT challenge (von Bezold‐Jarisch reflex). Using in vitroautoradiography, [3H]‐substance P was shown to bind to several regions of the ferret brainstem with the density of binding in the nucleus tractus solitarius being much greater than in the area postrema. This binding was displaced by CP‐99,994 in a concentration‐related manner. In dogs, CP‐99,994 (40 μg kg−1bolus and 300 μg kg−1h−1, i.v.) produced statistically significant reductions in vomiting to CuSO4and apomorphine as well as retching to CuSO4. Together, these studies support the hypothesis that the NK1receptor antagonist properties of CP‐99,994 are responsible for its broad spectrum anti‐emetic effects. They also suggest that CP‐99,994 acts within the brainstem, most probably within the nucleus tractus solitarius although the involvement of the area postrema could not be excluded.

We compare the “Lithium Activation” (LiA) method and the “Isospin Clebsch-Gordan Ratio” (ICGR) method for determining detection efficiencies of neutrons between 100 and 160 MeV. Each method was used to determine the efficiency by relating a measured neutron yield to a cross section measured in another way: γ-ray activation cross sections for LiA; (p, p′) cross sections from experiments at the Indiana University Cyclotron Facility for ICGR. Efficiencies determined by the two methods disagree substantially. Efficiencies calculated with the Monte Carlo code of Cecil et al. agree with the ICGR results. We conclude that the Lithium Activation method is inconsistent at these energies.