Solvatomorphism study of ergot alkaloids ergotamine and ergocristine

B. Klepetářová¹, J.Čejka¹, B. Kratochvíl¹, A. Jegorov², I. Císařová³

¹Department of Solid State Chemistry, Prague Institute of Chemical Technology, Technická 5

Prague 6, 166 28, Czech Republic, e-mail: blanka.klepetarova@vscht.cz, jan.cejka@vscht.cz, bohumil.kratochvil@vscht.cz

²IVAX Pharmaceuticals a.s., Research Unit, Branišovská 31, České Budějovice,

370 05, Czech Republic, e-mail: alexandr_jegorov@ivax-cr.com

³Department of Inorganic Chemistry, Charles University, Hlavova 8, Prague 2,

128 43, Czech Republic, e-mail: cisarova@natur.cuni.cz

Ergocristine and ergotamine are members of the large ergot alkaloids family. These pharmaceuticaly active substances are produced by parasitic funghi of the genus Claviceps purpurea. They are well known with their nonselective affinity to various dopamine, serotonin and α-adreno receptors. In their natural or chemically modified form ergot alkaloids are widely therapeutically used in medicine, e.g. in treatment of migraine, cognitive deterioration, cerebrovascular and many other diseases [1].

The investigation of polymorphism in pharmaceutical compounds is of utmost importance, as different polymorphs can have different pharmacokinetical profile and bioavailability.

New crystal structures – ergotamine bis(benzen) solvate and ergocristine bis(benzen) solvate were prepared and determined by single crystal X-ray diffraction. Conformations and molecular packing of these structures were compared with their solvatomorphs found in Cambridge Structural Database – ergotamine tartrate ethanol solvate [2] and ergocristine aceton solvate [3]. Comparison with semisynthetic derivatives - dihydroergotamines and dihydroergocristines was also carried out. Despite the chemical similarity, both studied structures differ not only in unit cell parameters, but they also exhibit quite different size and shape of solvent areas.

This work was partially supported in the frame of the research project CEZ: MSM 223100002 of Ministry of Education, Youth and Sports of the Czech Republic and projects No. 203/00/D095, No. 203/02/0436 and No. 203/99/M037 of the Grant Agency of the Czech Republic.

1. Z. Řeháček, P. Sajdl: Ergot Alkaloids: Chemistry, Biological Effects, Biotechnology. Praha 1990. ed. Academia.

2. S. Pakhomova, J. Ondráček, M. Hušák, B. Kratochvíl, A. Jegorov, J. Stuchlík: Acta Cryst., C51 (1995) 308.

3. S. Pakhomova, A. Jegorov, J. Ondráček, M. Hušák, B. Kratochvíl, V. Havlíček, L. Cvak, P. Sedmera: Z. Kristallogr., 211 (1996) 555.