Posttranslational changes in band 3 in adult and aging brain following treatment with ergoloid mesylates, comparison to changes observed in Alzheimer's disease
Life Sciences (USA) , 1996, 58/8 (655-664)
Band 3, the most heavily used anion transport system in vertebrates, ages as cells and tissues age. Posttranslational changes in band 3 in adult and aging brain were investigated following treatment with ergoloid mesylates and compared to changes observed in Alzheimer's disease (AD). The study was conducted in a double blind fashion and was decoded only after the study was completed. The following postranslational changes in brain band 3 occur with age: increased breakdown of band 3; decreased phosphorylation; and decreased anion transport. Autoantibodies to senescent cell antigen (SCA) synthetic peptides residue 538-554 and 812-827 increase with age, but antibodies to the former peptide are significantly reduced in ergoloid mesylate treated old mice. This is a critical transport region of band 3. Results showed that aged/altered band 3 increased in Alzheimer's disease (AD) as determined by quantitative antibody binding. Ergoloid mesylates altered the age-related posttranslational changes as follows: the observed age-related decrease in brain band 3 was partially reversed and anion transport was increased. This is consistent with the data indicating decreased autoantibodies to a critical anion transport segment of band 3. Aging appears to result in damage to a critical transport region of the anion transporter which is reflected by decreased anion transport, increased breakdown, alteration of the molecule itself, and an increase in autoantibodies to the region. Ergoloid mesylates seem to protect against this damage.
Hydergine revisited: A statistical analysis of studies showing efficacy in the treatment of cognitively impaired elderly
Age (USA) , 1995, 18/1 (5-9)
The pharmacologic treatment of dementia has received much attention in recent years. Hydergine, one of only two drugs approved by the Food and Drug Administration (FDA) for the treatment of dementia, was largely abandoned in the 1980's due to the uncertainty of its degree of clinical efficacy. The purpose of our study was to more precisely define the effect of Hydergine on cognitive function in elderly demented patients by combining the results of multiple weighted studies using similar methodology. All data came from randomized placebo controlled trials on a total of 271 subjects. Our results show that Hydergine had a statistically significant effect on global functional status compared to placebo, with the most significant improvement demonstrated on symptoms of depression, emotional lability, and indifference to surroundings. Further studies using Hydergine in the treatment of dementia appear to be justified.
Clinical study of Ternelin (R) therapy and Ternelin (R) and Hydergine (R) therapy for tinnitus
Practica Otologica (Japan) , 1995, 88/5 (645-656)
Patients with tinnitus were treated with Ternelin (R) (tizanidine hydrochloride) alone or in combination with Hydergine (R) (dihydroergotoxine mesylate). The following results were obtained. 1) When overal improvement was assessed at the end of the dosing period, 36% of the 136 patients who received Ternelin (R) and Hydergine (R) (the combined therapy group) showed moderate or marked improvement, while 61.8% of the patients in this group showed slight, moderate or marked improvement. The combined therapy was rated as moderately or highly useful in 35.3% and slightly to highly useful in 61% of all cases. 2) Of the 24 patients who received Ternelin (R) alone (the solo therapy group), 25% showed moderate or marked improvement, and 66.7% showed slight, moderate or marked improvement. Solo therapy was rated as moderately or highly useful in 25% and slightly to highly useful in 66.7%. 3) Of the 153 patients who received combined therapy (including 17 patients who were only included in the safety assessment), 9 developed adverse reactions (3 cases of drowsiness, and one each of orthostatic syncope, hypotonia, dizziness, gastric pain, constipation and oral thirst). None of the patients given Ternelin (R) alone showed any adverse reactions. 4) The percentage of cases showing marked or moderate improvement was higher in the combined therapy group than in the solo therapy group, although this difference was not significant. In the combined therapy group, the reduction in tinnitus peaked 2 to 4 weeks after the start of treatment. In the solo therapy group, the number of patients responding to the drug increased gradually with time, and more time was needed to obtain maximal effects than that in the combined therapy group.
Ergoloids and ischaemic strokes; Efficacy and mechanism of action
Journal of International Medical Research (United Kingdom) , 1995, 23/3 (154-166)
In this double-blind, randomized study the efficacy of the ergoloid compounds, co-dergocrine mesylate and nicergoline, in the rehabilitation of patients with ischaemic stroke was investigated. A group of 30 patients was treated daily with 60 mg nicergoline, orally, and a second group of 27 patients was given 1.8-6 mg co-dergocrine mesylate, orally or intramuscularly, daily (depending on the time since the initial ischaemic insult) for 6 months. Outcome measures included: motoricity index (limb function); Sandoz Clinical Assessment Geriatric (SCAG) scale; psychometric tests to assess functions such as attention, psychomotor performance, perception and sensory and short-term memory; conventional and computerized electroencephalography; and P300 and reaction time measures. The results showed improvements in some aspects such as limb function (P < 0.05), SCAG score (P < 0.01) and some electrophysiological parameters (P < 0.01) after treatment with both drugs. Though statistically significant most of the changes were not large. The efficacy of both drugs was qualitatively similar. The quantitative difference in some aspects in favour of nicergoline could be attributed to differences in the mechanisms of action of the two drugs, although it is also possible that the difference may reflect the dosages used. Nootropic drugs may induce a condition that facilitates the effects of cognitive training.
The effects of hydergine on the MAO activity of the aged and adult rat brain.
Eur Neuropsychopharmacol (NETHERLANDS) Dec 1995, 5 (4) p527-9
Despite the fact that hydergine has been used in the treatment of dementia for many years, its mechanism of action is still not clear. Current studies imply that the major effect of hydergine may be the modulation of synaptic neurotransmission rather than solely increasing blood flow as was once thought. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO) levels which results in decreased availability of catecholamines in the synaptic cleft. The aim of this study was to determine the effects of hydergine on the MAO activity in different brain regions (cortex, olfactory bulb, hypothalamus, hippocampus, striatum, cerebellum) of old (30 months) and adult (12 months) male Sprague-Dawley rats. In cortex and olfactory bulb MAO levels were higher in the aged group. In hippocampus and hypothalamus hydergine treatment caused significant decreases in MAO levels. An interaction between age and hydergine treatment was observed in the hypothalamus, hippocampus and cerebellum. The hydergine effect was more pronounced in the aged group in the hypothalamus and cerebellum, and more pronounced in the adult in the hippocampus. Our findings imply that increased brain MAO activity in aging can be modified by hydergine treatment in some brain regions.
Efficacy of pyritinol versus hydergine upon cognitive performance in patients with senile dementia of the Alzheimer's type: A double-blind multi-center trial
Alzheimer's Research (United Kingdom) , 1996, 2/3 (79-84)
In this multi-center trial, 100 patients with the diagnosis of Senile Dementia of the Alzheimer's type (SDAT) of mild to moderate severity were randomly divided into two treatment groups and, following a placebo wash-out phase, were administered either pyritinol or hydergine for 12 weeks in a double-blind, randomized parallel comparison. Two measures of cognitive functioning were employed to assess treatment effects. The results indicated that treatment with pyritinol was associated with a significant and continuous improvement in cognitive functioning over the course of the study while treatment with hydergine was associated with a more modest improvement that tended to plateau early in the treatment phase.