Two novel prolactin release-inhibiting 8α-amino-ergolines

Flückiger, E.; Briner, U.; Bürki, Hans R.; Marbach, Peter; Wagner, H.; Doepfner, W.

doi:10.1007/bf01953267

Cited by 31 publications

(10 citation statements)

References 7 publications

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“…The dopaminomimetic actions of several ergolines in vitro and in vivo are well established (Fliickiger et aL, 1979;Fliickiger et al, 1983;Fuxe et aL, 1983;Kebr, 1984;Wacbtel et aL, 1984;Markstein, 1983). Mesulergine has an unusual pattern in terms of its influence on DA metabolism.…”

Section: Discussionmentioning

confidence: 91%

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Dopaminergic properties of mesulergine (CU 32-085) and its metabolites

Enz¹,

Donatsch²,

Nordmann³

1984

J. Neural Transmission

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Mesulergine, an 8-alpha-aminoergoline, is now proven to be of utility in the clinic as an antiparkinsonian drug. However, the molecule itself shows in vitro and in vivo antidopaminergic properties. Mesulergine is rapidly metabolized into several pharmacologically active DA agonists. The influence of mesulergine on central DA metabolism in rats is dependent on the route of drug administration. It was possible to determine the different metabolites of this drug in plasma as well as in rat striatum. A correlation between the actual present concentration of the parent drug and DAergic metabolites and the net action on striatal DA metabolism was found. It may be concluded that mesulergine itself lacks DAergic activity but occupies DA receptors and is very rapidly metabolized into potent DA agonists.

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Section: Discussionmentioning

confidence: 91%

“…Mesulergine has an unusual pattern in terms of its influence on DA metabolism. A biphasic effect on DOPAC and HVA level in rat striatum was first described by Fliickiger et al (1979). The biphasic effect of mesulergine on DA turnover was not observed after either i.p.…”

Section: Discussionmentioning

confidence: 94%

Dopaminergic properties of mesulergine (CU 32-085) and its metabolites

Enz¹,

Donatsch²,

Nordmann³

1984

J. Neural Transmission

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“…The dopaminergic effects of several ergoline derivatives have been well established (30,35,52,90). Mesulergine, p.o.…”

Section: Pharmacologymentioning

confidence: 99%

Mesulergine: A Review

Galanopoulou

Giannakopoulos

1999

CNS Drug Reviews

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“…None of them inhibited ovum implantation in rats [5] at doses of 3 mg/kg S.C. (cf. 1 (CQ 32-084): ID,, = 0.028 mg/kg S.C. [6]). We conclude that the…”

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confidence: 99%

Synthesis of (5R,8S,10R)‐6‐(Allyloxy)‐ and (5R,8S,10R)‐6‐(Propyloxy)ergolines from the 6‐Methyl Precursors

Nordmann

Gull

1986

Helvetica Chimica Acta

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Ally1 bromide, K,CO,, DMF, 96 h, r.t. a) m-Chloroperbenzoic acid, CH,CI,, 1 h, ~ b) CH,CN, 45 min, reflux H,, 10% Pd/C, 16 h, r.t. CF,COOH, 30 min, r.t Et,NSO,CI, CHCI,, 16 h, 50°C -10°C; 91 % 85 % 65 % 64 % 53 % I1 % 59 % 53 % 29 % 25 Yo 31% 33 % Et,NCOCI, CHCI,, 16 h, 50°C HELVETICA CHIMICA ACTA -Vol. 69 (1986) Scheme 241 R' R' 3 CH, H 4 CH, Boc 5 CN Boc 6 H Boc 7 Ally1 Boc 7aWe report here the successful application of a Meisenheimer [2,3]-sigmatropic rearrangement [2] on a (5R,8S, lOR)-6-allyl-ergoline N6-oxide, which has ultimately led to analogues of 1 and 2 where N 6 has become part of a substituted hydroxylamine function. The Scheme illustrates our synthesis, whereas reaction conditions and chemical yields are summarized in the Table. 2. Synthesis. -To generate the substrate for the Meisenheimer rearrangement, 8aaminoergoline 3 [3] was first protected with (Boc),O to give 4, which was converted to ergoline 6 via 5 by an earlier developed modification of the uon Braun degradation [4].Alkylation to 6-allylergoline 7 (crystallized as hydrochloride) completed the first part of our synthesis. Oxidation of the free base 7 with m-chloroperbenzoic acid gave a polar product, presumably the "' -oxide 7a, which was not isolated but rearranged to 6-(allyloxy)ergoline 8a. Catalytic hydrogenation of 8a was surprisingly specific: the terminal double bond was hydrogenated without major cleavage of the N-0 bond to yield 6-propyloxyergoline 9a. The protecting group on the 8a -amino function was cleaved from both compounds 8a and 9a to give 8b and 9b, respectively, which were in turn converted to the derivatives 8c and 9c as well as 8d and 9d bearing the C(8) substituents of 1 and 2, respectively.The analytical data of all novel compounds are summarized in the Table, Section 1.3. Pharmacological Evaluation. -Compounds 8c, 8d, 9c, and 9d were evaluated for their pharmacological activity. None of them inhibited ovum implantation in rats [5] at doses of 3 mg/kg S.C. (cf. 1 (CQ 32-084): ID,, = 0.028 mg/kg S.C. [6]). We conclude that the

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Two novel prolactin release-inhibiting 8α-amino-ergolines

Cited by 31 publications

References 7 publications

Dopaminergic properties of mesulergine (CU 32-085) and its metabolites

Dopaminergic properties of mesulergine (CU 32-085) and its metabolites

Mesulergine: A Review

Synthesis of (5R,8S,10R)‐6‐(Allyloxy)‐ and (5R,8S,10R)‐6‐(Propyloxy)ergolines from the 6‐Methyl Precursors

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