Propisergide

Propisergide (INNTooltip International Nonproprietary Name; developmental code name PML-946), also known as ergalgin or as N-methylergometrine or 1-methylergometrine, is a serotonin receptor modulator and antimigraine agent of the ergoline and lysergamide families which was never marketed.^[2]^[3]^[4]^[5]^[6] It is the 1-methyl derivative of ergometrine (ergonovine) and is a close analogue of methylergonovine and methysergide (UML-491).^[7]^[5]^[8] Extensive metabolism of other 1-methylated lysergamides to their secondary amine derivatives, for instance methysergide (1-methylmethylergometrine) conversion into methylergometrine, has been observed.^[9]^[10] Propisergide has 259% of the antiserotonergic activity of LSD.^[7]^[1] Its average clinical dose range for preventative treatment of migraine is 1 to 3 mg orally.^[1] Propisergide was first described in the literature by 1958^[7]^[11] and then further around 1980 and after.^[6]^[12]^[13]

Other namesPML-946; PML946; Ergalgin; N-Methylergobasine; N-Methylergonovine; N-Methylergometrine; 1-Methylergonovine

Routes of
administrationOral^[1]

Drug classSerotonin receptor modulator; Antimigraine agent

ATC code

None

Quick facts Clinical data, Other names ...

Propisergide
Clinical data


Other names	PML-946; PML946; Ergalgin; N-Methylergobasine; N-Methylergonovine; N-Methylergometrine; 1-Methylergonovine
Routes of administration	Oral^[1]
Drug class	Serotonin receptor modulator; Antimigraine agent
ATC code	None
Identifiers
IUPAC name (6aR,9R)-N-[(2S)-1-hydroxypropan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide
CAS Number	5793-04-4
PubChem CID	20055549
ChemSpider	16737112
UNII	1Q1AWW2JET
ChEMBL	ChEMBL3989790
CompTox Dashboard (EPA)	DTXSID701018134
Chemical and physical data
Formula	C₂₀H₂₅N₃O₂
Molar mass	339.439 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C[C@@H](CO)NC(=O)[C@H]1CN([C@@H]2CC3=CN(C4=CC=CC(=C34)C2=C1)C)C
InChI InChI=1S/C20H25N3O2/c1-12(11-24)21-20(25)14-7-16-15-5-4-6-17-19(15)13(9-22(17)2)8-18(16)23(3)10-14/h4-7,9,12,14,18,24H,8,10-11H2,1-3H3,(H,21,25)/t12-,14+,18+/m0/s1 Key:XUKAVPATXGYVKJ-WPKBUWHJSA-N

References

[1]
Sicuteri F (October 1963). "Prophylactic Treatment of Migraine by Means of Lysergic Acid Derivatives". Triangle. 6: 116–125. PMID 14087164.
[2]
Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. ISBN 978-1-4757-2085-3. Retrieved 13 March 2025.
[3]
Ganellin CR, Triggle DJ (1996). Dictionary of Pharmacological Agents. Taylor & Francis. ISBN 978-0-412-46630-4. Retrieved 13 March 2025.
[4]
Waldman M, Fraczkiewicz R, Clark RD (September 2015). "Tales from the war on error: the art and science of curating QSAR data". Journal of Computer-Aided Molecular Design. 29 (9): 897–910. Bibcode:2015JCAMD..29..897W. doi:10.1007/s10822-015-9865-0. PMID 26290258.
[5]
Gelfand MD, West GB (1961). "Experimental studies with the butanolamide and propanolamide of 1-methyl-lysergic acid". Int Arch Allergy Appl Immunol. 18: 286–291. doi:10.1159/000229179. PMID 13704268.
[6]
Oelszner W (1980). "Displacement of specific serotonin and lysergic acid diethylamide binding by Ergalgin, a new antiserotonin drug". Acta Biologica et Medica Germanica. 39 (8–9): 897–901. PMID 7282219.
[7]
Doepfner W, Cerletti A (1958). "Comparison of lysergic acid derivatives and antihistamines as inhibitors of the edema provoked in the rat's paw by serotonin". International Archives of Allergy and Applied Immunology. 12 (1–2): 89–97. doi:10.1159/000228445. PMID 13549054.
[8]
"Propisergide". PubChem. U.S. National Library of Medicine. Retrieved 13 March 2025.
[9]
Majrashi M, Ramesh S, Deruiter J, Mulabagal V, Pondugula S, Clark R, et al. (2017). "Multipotent and Poly-therapeutic Fungal Alkaloids of Claviceps purpurea". In Agrawal DC, Tsay HS, Shyur LF, Wu YC, Wang SY (eds.). Medicinal Plants and Fungi: Recent Advances in Research and Development. Medicinal and Aromatic Plants of the World. Vol. 4. pp. 229–252. doi:10.1007/978-981-10-5978-0_8. ISBN 978-981-10-5977-3. ISSN 2352-6831. Metabolites of methysergide also exhibit pharmacological activity. Methylergometrine (one of methysergide's metabolites) is responsible for methysergide's therapeutic effects regarding migraine treatment (Müller-Schweinitzer and Tapparelli 1986). [...] The systemic availability of methysergide after oral administration is only 13%, due to a high degree of first-pass metabolism by N-1 demethylation to methylergometrine. After oral administration, the plasma concentrations of the metabolite are considerably higher than those of the parent drug, and the area under the plasma concentration curve (AUC) for methylergometrine is more than ten times greater than for methysergide.
[10]
Müller-Schweinitzer E, Tapparelli C (March 1986). "Methylergometrine, an active metabolite of methysergide". Cephalalgia. 6 (1): 35–41. doi:10.1046/j.1468-2982.1986.0601035.x. PMID 3698092. S2CID 5778173.
[11]
World Health Organization (1962). Cumulative List of Proposed International Non-proprietary Names for Pharmaceutical Preparations. 1962-. World Health Organization. ISBN 978-92-4-056013-0. Retrieved 13 March 2025. {{cite book}}: ISBN / Date incompatibility (help)
[12]
Bartsch R, Nowak R (January 1979). "Pharmacological Evaluation of a New Ergolin Derivative (Ergalgin)". Die Pharmazie. 34 (5–6). Eschborn, Germany: Govi-Verlag Pharmazeutischer GmbH: 358.
[13]
Harhammer R, Morgenstern R, Ott T (1992). "Pharmacological Effects of Ergalgin, a Potent Antagonist at Central and Peripheral 5-Ht (2) Receptors". Biogenic Amines. 8 (3–4): 267–275.

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