R-apomorphine

Grunblatt E, Mandel S, Maor G, Youdim MB. 2001. Gene e]q>ression analysis in N-methyl-4-phenyl- 1,2,3,6-tetrahydro-pyridine mice model of Parkinson s disease using cDNA microarray effect of R-apomorphine. J Neurochem 78 1. 

Figure 5. Relationship between (R,)-apomorphine and (+)-butaclamol/( dexclamol (5).

Vietri M, Vaglini F, Pietrabissa A, et al. Sulfation of R(—)-apomorphine in the human liver and duodenum, and its inhibition by mefenamic acid, salicylic acid and quercetin. Xenobiotica 2002 32(7) 587-594. 

Dopamine D2 activity of R-(-)-apomorphine and selected analogues a microdialysis study ... 

In the present study, R-(-)-apomorphine and three of its analogues were studied for their potency in decreasing the release of dopamine in the striatum after subcutaneous administration and for their oral bioavailability using the microdialysis technique in freely moving rats. 

This chapter is based on Rodenhuis, N. Dijkstra, D Vermeulen, E.S. Timmerman, W. Wikstrom, H.V. (2000) Dopamine D2 activity of R-(-)-apomorphine and selected analogs a microdialysis study. 

The dopamine D /D2 receptor agonist R-(-)-apomorphine has proven to be very effective in Parkinson s disease. Subcutaneously administered R-(-)-apomorphine in combination with L-DOPA rapidly and consistently reverses the off period motor deficits.253 256 Beside its action as a dopamine D,/D2 receptor agonist, R-(-)-apomorphine can also act as a radical scavenger257 and, therefore, may have neuroprotective properties. One of the major limitations of the clinical use of R-(-)-apomorphine, a catechol-aporphine, however, is its low oral activity. 

The drugs were dissolved in degassed ultra pure water with approximately 0.5 mg/ml ascorbic acid to prevent oxidation of the compounds and stocked in a concentration of 300 nmol/ml for subcutaneous administration and 10 pmol/2 ml for oral administration and diluted, if necessary, with degassed ultra pure water before administration. To dissolve R-(-)-ll-hydroxy-aporphine a drop of glacial acetic acid was added. Drugs used were R-(-)-apomorphine.HCl (11), R-(-)-ll-hydroxyaporphine (79), R-(-)-N- -... 

The dose-response relationships of the test compounds are given in Figure 5.2. The response of the compounds is given as the AUC. To compare the AUCs, the experiments were stopped after 180 min. The rank order in the potency upon s.c. administration of the compounds is R-(-)-N-//-propylnorapomorphine (80) > R-(-)- l 1 -hydroxy-N-//-propylnoraporphine (12) > R-(-)-apomorphine (11). 

Figure 5.2 Comparison of the dose-AUC relationship of R-(-)-apomorphine (11), R-(-)-N- -propylnorapomorphine (80) and R-(-)-l l-OH-N- -propylnoraporphine (12). Data represent mean values S.E.M. of 4 animals. Statistical analysis by t-test p<0.05, p<0.01, p<0.001. For comparison with R-(-)-apomorphine (11) 30 nmol/kg equal variance test failed and than Rank Sum Test followed by Mann-Whitney test was performed.

When the courses of the curves after s.c. administration of compounds 11, 80, and 12, respectively, are compared it can be seen that the duration of action of the N- -propyl analogues is longer than that of R-(-)-apomorphine. 

OH). Crystallise R-apomorphine from CHCI3 and a little pet ether, also from Et20 with 1 mol of Et20 which it loses at 100°. It sublimes in a high vacuum. It is white but turns green in moist air or in alkaline solution. UV ). tnax 336, 399 (98% EtOH). The di-O-methylether is an oil b 175°/high vacuum, whose picrate crystallises from MeOH and has m 140° (dec). The di-O-acetate crystallises from EtOAc/pet ether with m 127-... 

R-Apomorphine hydrochloride [41372-20-7] M 312.8, m 285-287"(dec), [a] -48° (c 1, H2O). Crystallise the salt from H2O (hemihydrate) and from EtOH. Crystals turn green on exposure to light, (see previous entry). NARCOTIC. 

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