Co-Dergocrine Mesylate

Abstract

Co-dergocrine mesylate is a combination of the mesylated forms of dihydroergocornine, dihydroergocristine, dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine. In animal models and healthy elderly volunteers the compound improves indices of cognitive function such as memory and learning. The mechanism(s) behind such action remains under investigation. Nonetheless, it has been proposed that co-dergocrine mesylate has a dual effect on central monoaminergic neurotransmitter systems, compensating for both hyperactivity and deficits of the adrenergic, serotoninergic and dopaminergic systems. The compound also appears to have a normalising effect on the power of electroencephalogram frequencies, and may improve cerebral metabolism. Results from controlled studies of elderly patients with age-related cognitive decline have established that co-dergocrine mesylate is well tolerated and, in some studies, had statistically significant positive effects on symptoms of cognitive dysfunction. However, there is considerable controversy over the clinical relevance of these results as there was wide variability in the number and type of cognitive and neuropsychological assessments used in individual studies and there may have been considerable overlap in diagnosis of patients with varying degrees of dementia. In addition, the drug has not been compared with most other, more recently developed, centrally active agents. Thus, the specific place of co-dergocrine mesylate in the treatment of age-related cognitive decline remains undetermined, despite many years of clinical use.

Pharmacokinetics of Dihydroergocristine and Its Major Metabolite 8- Hydroxy-Dihydroergocristine in Human Plasma

“…The apparent plasma DHEC t 1/2 determined by LC/MS/MS (3.5 h) agreed with those previously determined by RIA for DHEC [23] and dihydroergotoxine [4,24] after oral administration of corresponding tablets. Regarding data on 8'-OH-DHEC, it is worth emphasizing that the calculated plasma t 1/2 (3.9 h) did not follow dosing with metabolite, since it is the parent compound which is used in therapeutics.…”

Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic

“…In two studies (Aranda et al ., 1992; Milvio, 1992), dihydroergocristine was shown as safe and well tolerated with rare side effects including mild gastralgia, nausea, and dyspepsia in aged patients with senile dementia of Alzheimer type. Dihydroergocristine methanesulfonate in some studies has statistically significant positive effects on symptoms of age‐related cognitive dysfunction (Wadworth & Chrisp, 1992). …”