Serotonin inhibition of the NMDA receptor/nitric oxide/cyclic GMP pathway in human neocortex slices: involvement of 5-HT(2C) and 5-HT(1A) receptors.

The NMDA receptor/nitric oxide (NO)/cyclic GMP pathway and its modulation by 5-hydroxytryptamine (5-HT) was studied in slices of neocortical samples obtained from patients undergoing neurosurgery. The cyclic GMP elevation produced by 100 microM NMDA was blocked by 100 microM of the NO synthase inhibitor N(G)-nitro-L-arginine (L-NOARG) or by 10 microM of the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha] quinoxaline-1-one (ODQ). The NMDA effect was prevented by 5-HT or by the 5-HT(2) agonist (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane ((+/-)-DOI; EC(50)=22 nM). The (+/-)-DOI inhibition was insensitive to the 5-HT(2A) receptor antagonist MDL 100907 or the 5-HT(2B) antagonist rauwolscine; it was largely prevented by 1 microM of the non-selective 5-HT(2C) antagonists mesulergine (5-HT(2A,B,C)), ketanserin (5-HT(2A,C)) or SB 200646A (5-HT(2B,C)); it was completely abolished by 0.1 microM of the selective 5-HT(2C) receptor antagonist SB 242084. The NMDA-induced cyclic GMP elevation also was potently inhibited by the selective 5-HT(2C) agonist RO 60-0175 and by the antidepressant trazodone, both added at 1 microM, in an SB 242084-sensitive manner. Finally, the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 1 microM) inhibited the NMDA-evoked cyclic GMP response, an effect blocked by the selective 5-HT(1A) receptor antagonist WAY 100635. In conclusion, the NMDA receptor/NO/cyclic GMP pathway in human neocortex slices can be potently inhibited by activation of 5-HT(2C) or 5-HT(1A) receptors.

Disodium chromium(III) hexamolybdoiodate(VII) 24-hydrate, Na(2)Cr[IMo(6)O(24)].24H(2)O.

The title compound can be formulated as [Cr(H(2)O)(6)][Na(2)(H(2)O)(10)][IMo(6)O(24)].8H(2)O. The anion has the I atom on an inversion centre and has close to $\overline 3$m symmetry, with I-O bond lengths in the range 1.881-1.890 (2) A and Mo-O bond lengths in the ranges 1.697 (3)-1.714 (3), 1.915 (2)-1.948 (2) and 2.317 (2)-2.357 (2) A.

Inhibitory presynaptic 5-hydroxytryptamine(2A) receptors regulate evoked glutamate release from rat cerebellar mossy fibers.

We studied the pharmacological characterization of the 5-hydroxytryptamine(2) (5-HT(2)) heteroreceptor located on glutamatergic cerebellar mossy fiber nerve terminals. Depolarization-evoked overflow of endogenous glutamate from rat cerebellar "giant" mossy fiber synaptosomes was inhibited by 5-HT or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)-DOI], exhibiting pD(2) (= -log EC(50)) values of 7.37 and 7.29, respectively. Trazodone inhibited the depolarization-evoked glutamate overflow, exhibiting lower potency (pD(2) = 6.42) and lower efficacy with respect to 5-HT or (+/-)-DOI (maximal inhibition, 54%, compared with 70% for either 5-HT or (+/-)-DOI). Ketanserin, a 5-HT(2A)/5-HT(2C) receptor antagonist, counteracted the inhibitory effect of (+/-)-DOI or trazodone. Inhibition of glutamate overflow by 5-HT, (+/-)-DOI, or trazodone was prevented by the selective 5-HT(2A) receptor antagonist R-(+)-alpha-(2,3-dimethyoxyphenyl)-1-(2-(4-fluorophenyl)ethyl)-4-piperidine-methanol (MDL 100907), while the potent and selective 5-HT(2C) receptor antagonist 6-chloro-5-methyl-1-[6-(methylpyridin-3-yloxy)pyridin-3yl-carbamoyl] indoline (SB 242084) was ineffective. In cerebellar slices, MDL 100907 increased on its own the K(+)-evoked release of glutamate. It is concluded that the evoked release of glutamate from cerebellar mossy fibers can be controlled by inhibitory presynaptic 5-HT(2A) heteroreceptors, the receptors can be activated by endogenously released 5-HT, and trazodone behaves as a partial agonist at these receptors.