Detail of "94319-79-6"

Reference

Binding of [3H]Ro 16-6491, a reversible inhibitor of monoamine oxidase type B, to human brain mitochondria and platelet membranes

Binding of [3H]Ro 16-6491, a reversible inhibitor of monoamine oxidase type B, to human brain mitochondria and platelet membranes. Cesura, A. M.; Galva, M. D.; Imhof, R.; Da Prada, M. (Dep. Pharmacol., Univ. Milan, Italy). J. Neurochem., 48(1), 170-6 (English) 1987. CODEN: JONRA9. ISSN: 0022-3042. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The reversible inhibitor of monoamine oxidase (EC 1.4.3.4) [9001-66-5] type B (MAO-B) 3H-labeled Ro 16-6491 [N-(2-aminoethyl)-p-chlorobenzamide HCl] [94319-79-6] binds specifically and with high affinity to a single population of binding sites in human frontal cortex crude mitochondria and platelet membranes. In both tissues, binding equil. was reached after 1 h incubation at 20°. Dissocn. of bound radioactivity was relatively fast at 20°, whereas at 0°, [3H]Ro 16-6491 had the characteristics of a slowly dissocg. ligand. Inhibitors and substrates of MAO-B inhibited binding of [3H]Ro 16-6491, whereas MAO-A blockers were much less potent. Ro 16-6491 was also a substrate for MAO-B, and a stable unidentified intermediate of the oxidn. of Ro 16-6491 possessing high affinity for the enzyme may account for the marked MAO-B inhibitory effect of the drug. According to this hypothesis, Ro 16-6491 would behave as a mechanism-based reversible inhibitor. In conclusion, [3H]Ro 16-6491 binds selectively to MAO-B and represents an excellent new radioligand probe for studying the regional tissue distribution of this enzyme in normal and pathol. conditions.

Short-acting novel MAO inhibitors: in vitro evidence for the reversibility of MAO inhibition by moclobemide and Ro 16-6491

Short-acting novel MAO inhibitors: in vitro evidence for the reversibility of MAO inhibition by moclobemide and Ro 16-6491. Keller, H. H.; Kettler, R.Several substances are used for example 9001-66-5 and 71320-77-9 which are their cas registry numbers.; Keller, G.; Da Prada, M. (Pharm. Res. Dep., F. Hoffmann-La Roche and Co., Ltd., Basel CH-4002, Switz.). Naunyn-Schmiedeberg's Arch. Pharmacol., 335(1), 12-20 (English) 1987. CODEN: NSAPCC. ISSN: 0028-1298. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The inhibition of monoamine oxidase (MAO) [9001-66-5] in rat liver and brain by the short-acting MAO-A inhibitors Ro 11-1163 (moclobemide)(I) [71320-77-9] and brofaremine [63638-91-5] and the MAO-B inhibitors Ro 16-6491 (II) [94319-79-6] and almoxatone [84145-89-1], given orally at roughly equieffective doses 2 h before decapitation, was investigated. MAO A activity in liver homogenates, inhibited by moclobemide (300 mmol/kg) to approx.. 15% of control, time dependently recovered during 0.5-2 h of incubation at 37° irresp. of whether the homogenates were prepd. and incubated in distd. water or Krebs-Ringer buffer (KRB). Dialysis of such homogenates for 4 h in distd. water at 37° (but not at 13°) led to a complete return of the MAO activity. In liver homogenates from rats pretreated with brofaremine (30 mmol/kg), dialysis for 4 h at 37° against distd. water caused only little recovery of the MAO activity. Likewise, MAO-B inhibited by Ro 16-6491 (30 mmol/kg) to approx. 4% of control returned to almost control activity after 4 h of dialysis at 37°, whereas inhibition induced by almoxatone (30 mmol/kg) was slightly reversed or not at all. In brain homogenates prepd. in, and dialyzed against, distd. water or KRB at 37° (but not at 13°), MAO-A inhibited by moclobemide (100-300 mmol/kg) to approx. 15% of control, partially (KRB) or almost completely (distd. water) returned to control activity after 4 h of dialysis. From rats pretreated with Ro 16-6491 (30 mmol/kg), MAO-B in brain homogenates prepd. in KRB was reduced to 12% of control and returned to control value upon dialysis for 4 h in KRB at 37°; in homogenates prepd. in water, MaO-B was reduced to only 60% of control and completely recovered after dialysis against distd. water even at 13°. In all of these conditions, recovery of the enzyme activity was small after brofaremide and almoxatone. Analogous results were obtained with brain slices in KRB at 37°, whereby time-dependent recovery of MAO activity during incubation was achieved, and superfusion was somewhat more effective than incubation in restoring enzyme activity. In the expts. with incubated or superfused brain slices, inhibition of MAO-A and -B by the irreversible inhibitors clorgyline and selegiline (L-deprenyl), resp., could not be reversed at all. Tyramine clearly enhanced the recovery of MAO-A in KRB-prepd. liver homogenates and brain slices of moclobemide-pretreated rats but not in brain slices of brofaremide- and clorgyline-pretreated rats. Thus, the reversibility of MAO inhibition in vitro could be convincingly demonstrated for moclobemide and Ro 16-6491 but not for the other novel, short-acting MAO inhibitors studied. .