Nicergoline is an ergoloid mesylate derivative that is currently being used in the battle to treat senile dementia.
Interestingly it has been found to improve mental agility through enhancing
clarity and perception.
In this instance it is different to the effects of Hydergine -
(which improves oxygen stability, increases mental ability - i.e. it extends the
period of useful mental workload, and has been designated as an I.Q. booster
with its brain dendrite stimulation).
Nicergoline on the other hand appears to enhance clarity,
perception and clear thought.
Dosages for the treatment of senile dementia have been as high
as 30mg to 60mg daily, however treatment and protection from ARMD would normally
indicate 5mg once, twice or three times daily. Like nearly all nootropics,
nicergoline has been shown in clinical trials to be safe when used respectfully.
Side effects include nausea and headache, and is normally an
indication of over-dosage or over-stimulation through synergistic combinations.
If utilizing nicergoline with other nootropics, always reduce the individual
doses and only increase to larger doses over several days. Furthermore as with
all nootropic products occasional breaks are recommended (i.e. 1-week per month
or 2-days per week).
Tablets: Each tablet contains 5 mg
Nicergoline (I.N.N.). Excipients: Sucrose, calcium phosphate, sodium
carboxymethyl cellulose, micro-crystalline cellulose, magnesium stearate, gum
arabic, titanium dioxide, magnesium carbonate, flora wax, talc and Pal Super
Drops: Each ml (20 drops) of prepared solution contains: 5 mg
Nicergoline (I.N.N.), lactose, tartaric acid, methyparaben and water.
Sermion (nicergoline) is a vasoactive
pharmaceutical product, synthesized in Farmitalia research laboratories, with
alpha-adrenolytic action to activate the brain's metabolism. Sermion (nicergoline)
acts on different levels:
On the cerebral level, it prompts a lowering of
vascular resistance, an increase in arterial flow and the use of oxygen and
glucose. In terms of lung circulation, it lowers vascular resistance. With
regard to limb circulation, it brings about an increase in the flow,
particularly evident in those patients with insufficient irrigation due to
Studies carried out in vitro and in vivo, both
experimental and on human beings, have shown that Sermion (nicergoline)
inhibits platelet aggregation. Sermion (nicergoline) has proved to be
effective in hospital use, regulating and improving brain disorders caused by
metabolic-vascular insufficiency and alterations derived from insufficient
arterial irrigation in the limbs. When the therapeutic dosage is administered,
Sermion (nicergoline) does not affect arterial tension. In the case of
patients suffering from hypertension, it may induce a gradual lowering of
This pharmaceutical product does not induce
Acute and chronic cerebral metabolic-vascular
disorders (cerebral arteriosclerosis, thrombosis and cerebral embolism,
transitory cerebral ischaemia). Acute and chronic peripheral
metabolic-vascular disorders (organic and functional arteriopathies of the
limbs), Raynaud's disease and other syndromes caused by altered peripheral
Migraines of vascular origin
Coadjutant therapy in clinical situations
accompanied by platelet hyper-aggregability, arterial tension
Corio-retinal vascular disorders: retinal
thromboses, diabetic retinopathy, macular degeneration and retinal
angiosclerosis Oto-vestibular problems of a vascular nature: dizziness,
auditory hallucinations, hypoacusis.
By mouth: 5-10 mg (1-2 tablets or 20-40 drops)
3 times daily at regular intervals over prolonged periods of time. To
facilitate absorption, take this medicine between meals.
The dosage and length of treatment are to be
decided by your doctor. At times, the therapeutic effects of Sermion (nicergoline),
both subjective and objective, are not immediately noticeable, but will be
noted after a certain period of treatment.
Directions For Using Drops
Pour the powder into the vial containing the
solvent and shake until completely dissolved.
To measure out Sermion (nicergoline) in drops,
use the accompanying syringe, sucking in the amount of liquid required for
Although toxicology studies have not shown
nicergoline to have any teratogenic effect, the use of this medicine during
pregnancy should be limited to those cases where it is absolutely necessary.
The vasoactivity of Sermion (nicergoline) may
heighten the effect of pharmaceutical products that produce hypotension.
Although very infrequently, rubeosis, a hot
feeling, mild gastric upsets, hypotension and dizziness have been observed.
Should you notice any adverse reaction not described, consult your doctor or
Intoxication And Treatment
The chances of intoxication as a result of
taking this product are very remote. Only in certain cases of overdose can the
symptoms described under “Adverse Effects” appear. These subside if one
stops taking the product.
In cases of overdose or accidental ingestion,
consult the Toxicology Information Service.
Tablets: 45-tablet container. Drops: Container
with 1 vial of powder and 1 bottle of solvent.
This medicine must not be used after the expiry
date printed on the container.
Drops: Once prepared, the solution is good for
30 days at room temperature.
Keep this and all other medicines safely out of
the reach of children.
IN SENILE DEMENTIA OF ALZHEIMER TYPE AND MULTI-INFARCT DEMENTIA
Saletu B, et.al.
Pharmacia & Upjohn
In a double-blind, placebo-controlled study
on the therapeutic efficacy and central effects of nicergoline, an ergot
alkaloid with metabolic, antithrombotic and vasoactive action, 112 patients
with mild to moderate dementia, diagnosed according to DSM III-R criteria
(MMS 13-25), living in pensioners' homes, were included. Fifty-six were
subdiagnosed as senile dementia of the Alzheimer type (SDAT), 56 as
multi-infarct dementia (MID), based on computed tomography and Hachinski
scores ( < 49 SDAT, > 7 MID). They received, after 2
weeks' run-in period (placebo), randomized for 8 weeks either 2 x 30 mg
nicergoline (NIC) or 2 x 1 placebo (PLAC) orally. The four subgroups (SDAT/NIC,
SDAT/PLAC, MID/NIC, MID/PLAC; 4x28 patients) were comparable in regard to
age and sex. Only four, four, four and two patients of the respective groups
did not finish the study for minor reasons. Confirmatory sta alpha 2 and
beta activity and an acceleration of the centriod of the total power
spectrum as compared with pretreatment, while opposite changes occurred in
PLAC-treated SDAT and MID patients. The differences between PLAC and NIC
reached the level of statistical significance. Event-related potential (ERP)
recordings demonstrated a significantly shortened P300 latency under NIC
treatment in both SDAT and MID patients, while there was a trend towards
lengthening under PLAC. Thus, nicergoline improved vigilance and information
processing at the neurophysiological level, which leads at the behavioural
level to clinical improvement both in degenerative and vascular dementia.
In earlier studies involving clinical and
quantitative electroencephalographic (EEG) investigations in dementia
patients, we could demonstrate that both senile dementia of the Alzheimer type
(SDAT) and multi-infarct dementia (MID) patients demonstrated increased
delta/theta and decreased alpha and beta activity, as well as slowing of the
dominant frequency and the centroid of the total power spectrum, as compared
with normally ageing controls (Saletu et al. 1988, 1991a, 1992; Saletu 1994).
These alterations in brain function, evaluated initially by exploratory, and
later by confirmatory stastistics, reflected a deterioration in vigilance, as
defined first by Head in 1923 as the availability and grade of organization of
man's adaptive behaviour, which is dependent upon the dynamic state of the
neuronal network. This vigilance decrement results noopsychically in
deterioration of intellectual performance and memory, and thymopsychically in
decreased drive and affect, which constitute the axial syndrome of dementia,
as described in several psychiatric classification systems (Berner 1977;
American Psychiatric Association 1987). Indeed, utilizing correlation maps, we
could demonstrate that EEG slowing is correlated both to radiological and to
psychopathological and psychometric data: the more pronounced the atrophy in
computed tomography, the more delta and theta was evident at the
neurophysiological level, which in turn was correlated to higher SCAG and
lower Mini-Mental State scores at the clinical level, and to a poorer
psychometric performance, seen in several tests such as the Digit-Symbol
Substitution Test, the Trial-Making Test and the Digit Span Test (Saletu et
al. 1991a, b).
With regard to therapeutic efficacy in dementia
of the Alzheimer type and vascular dementia, several double-blind studies have
been carried out, partly with placebo, partly with active reference
substances. However, as some of these early studies have methodological
shortcomings in our present scientific methodological understanding, the
present study was carried out with a prospective allocation to a degenerative
(SDAT) and vascular aetiology (MID), and subsequent randomization of these
dementia sub-groups to placebo or verum. The aim of this double-blind,
placebo-controlled, parallel-group design study was to assess efficacy, safety
and neurophysiological effects of 30 mg nicergoline b.i.d. in mild to moderate
dementia of the Alzheimer type (SDAT) and multi-infarct dementia type (MID),
utilizing psychometric, computed tomography, EEG and ERP mapping technique.
Of the 112 demented patients included in the
study, only 14 dropped out prematurely. In the SDAT/NIC sub-group (n=28) four
patients dropped out after week 2 (two patients because they found the study
too troublesome. One because she required an antidepressant and one because
the moved to live with her daughter in another city). In the SDAT/PLAC
sub-group (n=28) four patients left the study in the wash-out period (one
because of a venous thrombosis in her legs, two because they found the
investigations too troublesome and one because she rejected the idea of taking
more pills). IN the MID/NIC sub-group (n=28) four patients with drew from the
study (two in the wash-out period, one in week 2 and one in week 4 because
they found the study too troublesome). In the MID/PLAC sub-group (n=28), two
patients withdrew in the wash-out period because they found it too tiresome to
If one calculates the percentage of responders
and non-responders in all four sub-groups, 66.6 per cent of nicergoline-treated
SDAT patients showed improvement and 33.3 per cent a non-response, while the
placebo-treated SDAT patients exhibited just the opposite findings. Similarly,
70.83 per cent of the nicergoline-treated MID patients were responders, 29.17
per cent non-responders, while of the placebo-treated MID patients 73.08 per
cent were non-responders and 26.92 per cent responders. The differences
between the groups were significant.
EEG maps -- multi-variate analysis
In order to obtain an answer to the question of
whether or not the investigational drug exerted a significant effect on the
human brain as compared with placebo, MANOVAs were performed (for each of the
21 electrodes) considering drugs (nicergoline, placebo), times (weeks 0 and 8)
and variates (nine absolute power and nine frequency measures). Absolute power
values were transformed in In(power) to fulfil the conditions for the MANOVA
(homogeneity of variances and co-variances), as well as the symmetrical
unimodal distribution (Gasser et al. 1982). Hotelling's T2 values were used to
avoid type 1 errors, with inflated df, and were imaged in terms of brain maps
(Fig.1). As can be seen, nicergoline induced, as compared with placebo,
significant changes in brain function in both SDAT and MID patients.
EG MAPS - UNIVARIATE ANALYSIS
In the placebo-treated SDAT patients, absolute
power increased in the delta/theta and slow alpha, as well as in the
superimposed beta frequency range, while opposite changes as well as a
decrease of alpha-2 activity occurred in the nicergoline-treated patients
(P<0.05, t-test). Thus, inter-drug differences revealed a significant
attenuation of delta/theta, alpha-1, but also alpha-2 and beta power, after
nicergoline as compared with placebo (P<0.05 t-test).
Relative power increased in the delta/theta and
alpha-1 frequency bands of placebo-treated SDAT patients, along with a
decrease of alpha-2 and beta activity, while nicergoline-treated patients
showed exactly the opposite (P<0.05) (Fig.2). Thus, nicergoline induced, as
compared with placebo, an attenuation of delta/theta and slow alpha and an
augmentation of alpha-2 and beta activity (P<0.05) (Fig.2). These
alterations, reflecting an improvement in vigilance, were most pronounced over
the right temporal to frontotemporal and left parietal and temporo-occipital
The centroids became faster in the delta/theta
and slower in the alpha, beta and total frequency bands after 8 weeks' placebo
in SDAT patients, while an alpha acceleration and acceleration of the total
centroid occurred after nicergoline treatment (P<0.05-0.01). Thus,
inter-drug differences were characterised by an acceleration of the alpha,
beta and total centroid after nicergoline, as compared with placebo, while the
delta/theta centroid slowed down (P<0.05).
In MID patients, a decrease in absolute power
occurred in the beta band after placebo (P<0.05), while a trend towards an
attenuation of delta/theta power was observed after nicergoline. There were no
significant inter-drug differences.
Relative power showed an increase in the
alpha-1 and decrease in the beta range after placebo administration, while
after nicergoline delta/theta attenuation and alpha-1 and -2 augmentation
occurred (P<0.05) (Fig.3). Inter-drug differences were characterized by an
attenuation of delta/theta power and augmentation of alpha-2 and beta power
(P<0.05), thereby signalling an improvement of vigilance (Fig.3).
The centroids showed a slowing in the alpha,
beta and total frequency range after placebo (P<0.05), while an opposite
trend occurred after nicergoline. Thus, nicergoline induced, as compared with
placebo, an acceleration of the alpha centroid and total centroid, while in
regard to the beta centroid there was an acceleration over the left parietal
and occipito-temporal region and a slowing over the right fronto-temporal
EVENT RELATED POTENTIAL FINDINGS (P300)
While in both SDAT and MID patients nicergoline
induced a significant (P<0.05, t-test) shortening of latency of the P300, a
trend towards lengthening occurred after 8 weeks of placebo treatment.
Differences between verum and placebo were significant (P<0.05) in both
sub-types of dementia. Thus, the significantly shortened latency in both
sub-types of dementia suggests an improved cognitive information processing
This double-blind, placebo-controlled study
demonstrated that nicergoline improved the clinical symptomatology of both
SDAT and MID patients, as compared with placebo. The superior therapeutic
efficacy of nicergoline after 8 weeks of treatment with 30 mg b.i.d. over
placebo was clearly demonstrated in the confirmatory statistical analysis for
the target variable, the clinical global impression, with the clinical
relevance of this outcome underlined by the results of the descriptive
statistics in the other investigated variables, further by the responder
analysis, as well as by the neurophysiological findings underlying the
The Clinical Global Impression (CGI) changes
were, of course, of small magnitude, with the patients remaining still
moderately ill, as far as the severity of illness was concerned. However, item
2 of the CGI showed, on average, a slight improvement in the nicergoline-treated
SDAT and MID patients, while there was no change on average after placebo.
Moreover, the responder analysis demonstrated that 66.6 per cent of SDAT
patients treated with nicergoline improved, while 33.3 per cent did not
improve, with just the opposite findings under placebo administration (33.3
per cent improving; 66.6 per cent not improving). Very similarly, with
nicergoline treatment of MID patients, 71 per cent improved, 29 per cent did
not, while under placebo administration 27 per cent improved and 73 per cent
did not. Other nootropic durgs have also been reported to exert similar
therapeutic effects in MID and SDAT patients (Saletu et al. 1988, 1992;
Fischhof et al. 1989, 1992).
Nicergoline was very well tolerated, as mild
side-effects, such as itching, blocked nose, headaches, tachycardia, sweating,
insomnia, dry mouth, diarrhoea, constipation and weight loss were mostly
observed only in single patients. Oveerall, they were of transient nature and
did not warrant any treatment. This low incidence (19 per cent in the
nicergoline-treated patients versus 15 per cent in the placebo-treated ones)
is in agreement with open-field studies, which also showed a decrease in
frequency in virtually all categories of complaints with time (13 per cent in
week 4 versus 4.3 per cent in week 24) (Saletu 1991).
Finally, in the light of the significant
nicergoline induced improvement observed in the Mini-Mental State in regard to
cognition, it seems of interest that the cognitive evoked potential -- the
P300 -- showed a significantly shortened latency in nicergoline-treated SDAT
and MID patients, while placebo-treated ones exhibited a trend towards
lengthening. Several authors such as Squires et al. (1980), Semlitsch et al.
(1990, 1992) and Polich (1991) pointed out that the P300 can provide useful
information on individual cognitive function. It may possibly be more than a
coincidence that the shortening of the P300 latency under nicergoline in SDAT
and MID patients (in ms) is the same as the amount by which the latency of the
untreated dementia patients deviates from that of normal aged subjects (Saletu
1994). Thus, nicergoline siginificantly improved stimulus evaluation time of
cognitive information processing, thereby tending to normalize the former in
both SDAT and MID patients.
The authors would like to express their thanks
to Drs. E. Kaplan, E. Herchenhan and D.H. Meier from Pharmacia, Germany, and
Dr. Ch. De Paolis from Pharmacia, Milan; further to Dr. Wuschitz, H. Saulean
and D. Rabel as well as to K. Decker and G. Binder for researach assistance:
to Dawn Eckelhart, Secretary; to Helmut Bernhardt, Medical Illustrator and
Photographer as well as to the entire of the Division of Pharmacopsychiatry,
Department of Psychiatry and the SPECT Laboratory, Department of Neurology,
School of Medicine, University of Vienna and the Institute of Neuroimaging,
Rudolfinerhaus, Vienna, for their great assistance in this project.
In particular, the authors would also like to
thank H. Dinhof, Acting Director of the Kuratorium der Wiener
Pensionistenheime and the physicians, staff and patients of the Viennese Old
Age Pensioners' Homes, especially the Pensionistenheime Rosenberg and
Hetzendorf for their valuable support