Neurochemical and Neuropharmacological Investigations with Four Ergot Derivatives: Bromocriptine, Dihydroergotoxine, CF 25-397 and CM 29-712

Abstract

Neurochemical and neuropharmacological investigations with four ergot derivatives reveal differential pharmacodynamic effects of these compounds. Bromocriptine and CM 29–712 showed actions typical of postsynaptic dopamine receptor stimulants, in particular in the extrapyramidal system. CM 29–712 proved to be more potent than bromocriptine, with an early onset of action. CF 25–397 and dihydroergotoxine, while not showing all actions typical of central dopamine agonists, appeared to exert some of their effects by means of a stimulation of central serotoninergic sites. In the rat sleep-wakefulness cycle and in reserpine-induced ponto-geniculo-occipital waves in the cat, they mimicked the effects of 5-hydroxytryptophan. In the latter test, CF 25–397 proved to be particularly potent. In addition, bromocriptine, dihydroergotoxine and CM 29–712 showed neurochemical effects consistent with central α-adrenergic blockade or an enhanced impulse flow in central noradrenergic neurons.

Catecholamine Turnover in Rat Cerebral Cortex and Caudate following Repeated Treatment with Dihydroergotoxine

“…In the caudate, DA turnover was changed only after long-term (10 days) DHETX treatment, showing an increased metabolism of this catecholamine. It has been shown previous ly that DHETX at dosages of 10 and 100 mg/kg exerts actions typical of central dopamine ago nists (5,22). The present data point to a possible antagonistic effect of DHETX on DA receptors in the caudate following repeated treatment with the drug.…”

“…Repeated appli cation of the drug produces accumulation of DHETX in the rat cerebral cortex (15). It seems that stimulation of extrastriatal dopaminergic receptors occurs only after high DHETX dosage (5,22). In the caudate, DA turnover was changed only after long-term (10 days) DHETX treatment, showing an increased metabolism of this catecholamine.…”

“…Ljubljana (Yugoslavia). DHETX, an ergolene derivative composed of dihydroergocornine, dihydroergocristine and dihydroergocriptine in equal proportions, exerts a number of metabolic effects in the brain (14, 16), among which are also the effects on the level and metabolism of biogenic amines (5,22).DHETX exerts complex effects on the cen tral nervous system that are different from those of known stimulants. The results of Loew et al (12) suggest that DHETX might act as a dopamine agonist at the level of the pontomedullary reticular formation; treatment with DHETX at a dose of 1 mg/kg, found to be…”

“…In the previous studies (5,22), the metabo lism of norepinephrine (NE) was evaluated in the brain stem and that of dopamine (DA) in the striatum; the dosage of DHETX (10 and lOOmg/kg, i.p.) used in the above-mentioned experiments was fairly high and of less clinical significance.…”

Key Enzymes of Glycolysis in Rat Brain: Effects of Single and Repetitive Treatment with Dihydroergotoxine (Redergin®)

“…The majority of biochemical investigations were concerned with catecholamine metabolism and the related cyclic AMP system (2,3,10,12,21). Also, DHETX expresses the beneficial ef fects on the brain damaged by hypoxia and ischemia (1,2,4,14), and these effects are more pronounced during recovery after short term ischemia (5,15).…”