Central nervous system drugs: Low temperature X-ray structures of (I) the base 5-(2,3-dichlorophenyl)-2,4-diamino-6-fluoromethyl-pyrimidine (4030W92) and (II) 5-(2,6-dichlorophenyl)-1-H-2,4-diamino-6-methyl-pyrimidine methanesulphonic acid salt (227C89)

The X-ray crystal structures of (I), the base 4030W92, 5-(2,3-dichlorophenyl)-2,4-diamino-6-fluoromethyl-pyrimidine, C11H9Cl2FN4, and (II) 227C89, the methanesulphonic acid salt of 5-(2,6-dichlorophenyl)-1-H-2,4-diamino-6-methyl-pyrimidine, C11H11Cl2N4 center dot CH3O3S, have been carried out at low temperature. A detailed comparison of the two structures is given. Structure (I) is non-centrosymmetric, crystallizing in space group P2(1) with unit cell a = 10.821(3), b = 8.290(3), c = 13.819(4) angstrom, beta = 105.980(6)degrees, V = 1191.8(6) angstrom(3), Z = 4 (two molecules per asymmetric unit) and density (calculated) = 1.600 mg/m(3). Structure (II) crystallizes in the triclinic space group P (1) over bar with unit cell a = 7.686(2), b = 8.233(2), c = 12.234(2) angstrom, alpha = 78.379(4), beta = 87.195(4), gamma = 86.811(4)degrees, V = 756.6(2) angstrom(3), Z = 2, density (calculated) = 1.603 mg/m(3). Final R indices [I > 2sigma(I)] are R1 = 0.0572, wR2 = 0.1003 for (I) and R1 = 0.0558, wR2 = 0.0982 for (II). R indices (all data) are R1 = 0.0983, wR2 = 0.1116 for (I) and R1 = 0.1009, wR2 = 0.1117 for (II). 5- Phenyl-2,4 diaminopyrimidine and 6-phenyl-1,2,4 triazine derivatives, which include lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine), have been investigated for some time for their effects on the central nervous system. The three dimensional structures reported here form part of a newly developed data base for the detailed investigation of members of this structural series and their biological activities.

Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

In addition to its hyperphagic effect in rats, 8-OH-DPAT also reduces grooming, but it is uncertain whether the inhibition of grooming is a specific effect or a consequence of response competition from eating. The present experiments explored the effects of 8-OH-DPAT on periprandial grooming and grooming elicited by spraying rats with water. Momentary time sampling over 30 or 60 min, with behaviour scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face grooming, body grooming, genital grooming and resting) at 15s intervals, was used for data collection. Non-deprived rats were tested in the presence and absence of food and baseline grooming levels were manipulated by spraying the dorsal surface of the back with water. Data were submitted to ANOVA. The first experiment confirmed that 8-OH-DPAT increased food intake and that this was associated with a parallel increase in feeding observations; active observations were also increased, but resting and total grooming observations were reduced: scratching was reduced even at 0.003mg/kg, face- and body-grooming were reduced at doses > 0.03mg/kg and genital-grooming was least sensitive, only being reduced at 0.1mg/kg. The second experiment revealed that spraying with water had no effect on food intake, feeding or resting observations, but increased total grooming (largely due to increased body-grooming) and reduced activity observations. In rats sprayed with water, 8-OH-DPAT increased food intake (0.1mg/kg) and observations of feeding (0.003 & 0.1mg/kg), but total grooming was dose-dependently inhibited, with genital-grooming most sensitive(> 0.003mg/kg), followed by face-grooming (> 0.01mg/kg) and body-grooming (>0.03mg/kg), whilst low levels of scratching were unaffected. The final experiment tested water-sprayed rats in the absence of food: 8-OH-DPAT increased resting and reduced total grooming, mostly as a consequence of reductions in face- and body-grooming, but there were also modest reductions in scratching. These results confirm that 8-OH-DPAT has a suppressant effect on all aspects of grooming, except where there are probable floor effects, and that this is independent of response competition from increased eating.

Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

The effects of 8-OH-DPAT treatment on rat grooming behaviour, elicited either prandially or in response to spraying with water were investigated. Dose (≤0.1 mg/kg s.c.) response studies employed momentary time sampling over 30 or 60 min with behaviour being scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face-grooming, body grooming, genital-grooming and resting) at 15 s intervals. In non-deprived rats, tested with wet mash available, feeding and activity frequencies were increased, but resting and total grooming were inhibited by 8-OH-DPAT. Face-, body- and genital-grooming occurred at higher levels than scratching, but all categories were reduced with reductions in scratching occurring at a lower dose (0.01 mg/kg). Misting rats with a fine water spray selectively increased body grooming and decreased activity without altering feeding, while 8-OH-DPAT increased feeding and reduced face-, body- and genital-grooming, without affecting already low levels of scratching. In misted rats, tested without food, 8-OH-DPAT reduced face-, body- and genital-grooming and increased resting. These results confirm i) that the water spray technique is a useful method for increasing grooming and ii) that 8-OH-DPAT has a suppressant effect on grooming independent of response competition from enhanced feeding.

Sediment transfer and accumulation in two contrasting salt marsh/mudflat systems: the Seine estuary (France) and the Medway estuary (UK)

Understanding the dynamics of fine sediment transport across the upper intertidal zone is critical in managing the erosion and accretion of intertidal areas, and in managed realignment/estuarine habitat recreation strategies. This paper examines the transfer of sediments between salt marsh and mudflat environments in two contrasting macrotidal estuaries: the Seine (France) and the Medway (UK), using data collected during two joint field seasons undertaken by the Anglo-French RIMEW project (Rives-Manche Estuary Watch). High-resolution ADCP, Altimeter, OBS and ASM measurements from mudflat and marsh surface environments have been combined with sediment trap data to examine short-term sediment transport processes under spring tide and storm flow conditions. In addition, the longer-term accumulation of sediment in each salt marsh system has been examined via radiometric dating of sediment cores. In the Seine, rapid sediment accumulation and expansion of salt marsh areas, and subsequent loss of open intertidal mudflats, is a major problem, and the data collected here indicate a distinct net landward flux of sediments into the marsh interior. Suspended sediment fluxes are much higher than in the Medway estuary (averaging 0.09 g/m(3)/s), and vertical accumulation rates at the salt marsh/mudflat boundary exceed 3 cm/y. Suspended sediment data collected during storm surge conditions indicate that significant in-wash of fine sediments into the marsh interior can occur during (and following) these high-magnitude events. In contrast to the Seine, the Medway is undergoing erosion and general loss of salt marsh areas. Suspended sediment fluxes are of the order of 0.03 g/m(3)/s, and the marsh system here has much lower rates of vertical accretion (sediment accumulation rates are ca. 4 mm/y). Current velocity data for the Medway site indicate higher velocities on the ebb tide than occur on the flood tide, which may be sufficient to remobilise sediments deposited on the previous tide and so force net removal of material from the marsh.

X-ray crystallographic structures of neuroprotective pyrimidine derivatives: (I) the mesylate salt of BW1003C87 and (II) sipatrigine base

Drugs based on 5-phenyl-2,4 diamino pyrimidine and 6-phenyl-1,2,4 triazine derivatives are well known for their effects on the central nervous system. The study presented here provides detailed crystal structures of two pyrimidine derivatives which have neuroprotective properties in models of both grey and white matter ischemia. Recently published studies suggest that the compounds lamotrigine (a triazine derivative), and the two pyrimidines BW1003C87 (I) and sipatrigine (II) mediate their primary in vivo mode of action by inhibiting voltage-gated Na+ channels. The X-ray crystal structures will contribute valuable data for applications involving binding and modelling studies of the biological actions of these drugs.