Dihydroergocryptine

Structural formula
General
Non-proprietary name	Dihydroergocryptine
other names	α-dihydroergocryptine (α-DHEC); (5'a, 10a) -9,10-dihydro-12'-hydroxy-2 '- (1-methylethyl) -5' - (2-methylpropryl) -ergotaman-3 ', 6', 18-trione ( IUPAC ) ;
Molecular formula	C 32 H 43 N 5 O 5
External identifiers / databases
EC number	246-993-6
ECHA InfoCard	100.042.706
PubChem	114948
ChemSpider	102887
DrugBank	DB11274
Wikidata	Q905717
Drug information
ATC code	N04 BC03
Drug class	Dopamine agonist
properties
Molar mass	577.72 g mol −1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Dihydroergocryptine (DHEC) is a drug derived from ergot alkaloids . It acts primarily as a dopamine D ₂ agonist and also as a D ₁ partial agonist and is mainly used to treat Parkinson's disease .

Clinical information

Application areas (indications)

Parkinson's disease, in patients with no fluctuations in the clinical picture as monotherapy or in combination with levodopa .
Interval treatment of migraine headaches (Switzerland only).

Dosis, kind and Time of the Use

Parkinson's disease

The starting dose is 10 mg per day (mg / d). After two weeks, an increase of 10 mg / day can be made until the required maintenance dose is reached. The maintenance dose is i. d. Usually 60 mg / d and in individual cases up to 120 mg / d. These dosages also apply to combination treatments with levodopa. The daily dose is to be divided into two doses.

Migraine headache

The interval treatment for migraine headaches is started with a dose of 10 mg / day and can be increased to the maintenance dose of 20 mg / day after two weeks. Even if the treatment is successful, the use of DHEC should be interrupted after six months and only restarted in the event of a relapse. The daily dose is to be divided into two doses.

Contraindications (contraindications)

Hypersensitivity to ergot alkaloids
advanced liver damage
Combination treatment with erythromycin and other macrolide antibiotics , which the cytochrome P450 - isoenzyme cytochrome P450 3A4 inhibit
Childhood
pregnancy and breast feeding period

Particular caution is required with psychoses and high blood pressure

Drug interactions

Inhibitors of the drug-degrading enzyme CYP 3A4 lead to a significant increase in the blood level of DHEC: in a study with erythromycin , the peak blood levels increased by about 10-fold; overall there was a 16-fold increase in the availability of DHEC in the blood. Therefore, erythromycin and other macrolide antibiotics should not be given with DHEC. Caution should also be exercised when concomitantly treated with other inhibitors of the CYP-3A4 enzyme (e.g. HIV protease inhibitors , azole antifungal agents , verapamil , valproic acid , fluoxetine , cimetidine or amiodarone ). When these drugs are stopped again, the dose of DHEC may need to be adjusted again.
DHEC should not be used together with other ergot alkaloids, as the side effects of these drugs can be increased ( ergotism ).
DHEC can impair platelet aggregation and have an anticoagulant effect. More frequent controls should be carried out in patients who are also receiving other medicinal products that affect blood clotting .
An interaction between DHEC and drugs that affect blood pressure or the psyche cannot be ruled out. Interactions with alcohol have not been studied. Simultaneous consumption of alcohol can impair the tolerance of DHEC.
The simultaneous use of nitro preparations can u. U. increase the effect of DHEC.
DHEC has no clinically relevant effect on the pharmacokinetics of levodopa. However, if levodopa is used at the same time, stomach pain, low blood pressure, headache and edema may occur more frequently .

Use during pregnancy and breastfeeding

Animal studies have shown undesirable effects on the fetuses . DHEC can induce labor before the date of pregnancy and can inhibit milk delivery . Therefore, DHEC should not be used during pregnancy or while breastfeeding.

Other Information

history

DHEC was developed in the 1990s by the Italian company Poli (now Polichem SA, Lugano, Switzerland) in the areas of Parkinson's disease and migraine and then out-licensed to various companies in Germany and Switzerland.

Studies

The approval of DHEC in the treatment of patients with Parkinson's disease is based on studies by Battistin et al . and Bergamasco et al. Efficacy in treating migraines has been confirmed by Bussone et al and Micieli et al. Like many dopamine agonists , DHEC has been studied in the treatment of patients with restless legs syndrome (RLS). However, DHEC is not approved for the treatment of RLS.

Trade names

Almirid (D), Cripar (D, CH)

Individual evidence

↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ C. de Mey, M. Althaus, E. Ezan, A. Retzow: Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans. In: Clin Pharmacol Ther . 70, 2001, pp. 142-148. PMID 11503008
↑ L. Battistin, PG Bardin, F. Ferro-Milone et al: Alpha-dihydroergocryptine in Parkinson's disease: a multicenter randomized double blind parallel group study. In: Acta Neurol Scand. 99, 1999, pp. 36-42. PMID 9925236
↑ B. Bergamasco, L. Frattola, A. Muratorio et al .: Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results of a multicentre, randomized, double-blind, placebo-controlled study. In: Acta Neurol Scand. 101, 2000, pp. 372-380. PMID 10877152
↑ G. Bussone, R. Cerbo, N. Martucci et al: Alpha-dihydroergocryptine in the prophylaxis of migraine: a multicenter double-blind study versus flunarizine. In: Headache. 39, 1999, pp. 426-431. PMID 11279920
↑ G. Micieli, A. Cavallini, S. Marcheselli et al: Alpha-dihydroergocryptine and predictive factors in migraine prophylaxis. In: Int J Clin Pharmacol Ther . 39, 2001, pp. 144-151. PMID 11332869
↑ F. Tergau, p wiper, C. Wolf, W. Paul: Treatment of restless legs syndrome with the dopamine agonist alpha-dihydroergocryptine. In: Mov Disord. 16, 2001, pp. 731-735. PMID 11481700 .

[NV-1] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[2] C. de Mey, M. Althaus, E. Ezan, A. Retzow: Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans. In: Clin Pharmacol Ther . 70, 2001, pp. 142-148. PMID 11503008

[3] L. Battistin, PG Bardin, F. Ferro-Milone et al: Alpha-dihydroergocryptine in Parkinson's disease: a multicenter randomized double blind parallel group study. In: Acta Neurol Scand. 99, 1999, pp. 36-42. PMID 9925236

[4] B. Bergamasco, L. Frattola, A. Muratorio et al .: Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results of a multicentre, randomized, double-blind, placebo-controlled study. In: Acta Neurol Scand. 101, 2000, pp. 372-380. PMID 10877152

[5] G. Bussone, R. Cerbo, N. Martucci et al: Alpha-dihydroergocryptine in the prophylaxis of migraine: a multicenter double-blind study versus flunarizine. In: Headache. 39, 1999, pp. 426-431. PMID 11279920

[6] G. Micieli, A. Cavallini, S. Marcheselli et al: Alpha-dihydroergocryptine and predictive factors in migraine prophylaxis. In: Int J Clin Pharmacol Ther . 39, 2001, pp. 144-151. PMID 11332869

[7] F. Tergau, p wiper, C. Wolf, W. Paul: Treatment of restless legs syndrome with the dopamine agonist alpha-dihydroergocryptine. In: Mov Disord. 16, 2001, pp. 731-735. PMID 11481700 .