Clinical and Technical Aspects
procedures were carried out in the following way:
testing ( 1982 – 1990 ) on laboratory animals
to prove safe
use of preparation, indicated that the SEMAX®
is free from hormonal or doping effects, is not toxic, does
not evoke the habituation syndrome and meets the standards and
requirements for use in public health.
Trials ( 1990-1994 ).
303 patients were tested in Military
hospitals. 200 patients were treated with SEMAX®
and 103 patients were treated with conventional treatment (without
A double–blind placebo controlled- type test was applied
on 59 patients, among whom one group of patients was administered
SEMAX® and the other group a placebo.
This trial, which lasted for 4 years, proved that SEMAX®
could be used in hospitals and polyclinics for treatment and
rehabilitation of patients with intellectual and memory disturbances,
and to improve the mental working capacities of normal, healthy
persons working under great mental and physical stress conditions
Trials ( 1994-1996 ).
These Trials lasted 2 years and involved several thousand patients
in medical centers around the Russian Federation.
It was shown that SEMAX® met all standards
and requirements for use in public health, and its mode of action
as a neuroactive regulatory peptide was achieved without evoking
any side effects.
The neuroactive properties of short fragments of ACTH (Adenocorticotropic
Hormone) are well documented. The Dutch scientists D
de Wied and J.Jolles, Van
Reizen et al, observed non-specific activation of the
brain, in which non-specific processes of memory (motivation,
attention, sensitivity/irritability) are strengthened, or to
the inclusion of fragments of ACTH into specific memorizing
processes (consolidation, strengthening of memory).
the fragment ACTH(4-10) (Met-Glu-His-Phe-Arg-Trp-Gly)
scientists discovered through the process of dissociation of
the amino acids and utilizing substitution and special linkages,
a peptide which was free from any hormonal effects but possessed
neuroactive endogenous modulatory and regulatory properties,
the sum of which manifested in a significant neuroprotective
effect against ischemic insults.
compound which was named SEMAX® consisted
of the bioactive portion of
ACTH4-10, : Met-Glu-His-Phe, and the substitution of
Arg-Trp-Gly with: Pro-Gly-Pro.
The P-G-P binding resulted in much improved stability due to
increased resistance towards blood peptidases.
In essence the molecule became :
Pro8-Gly9-Pro10 ACTH(4-10) or ACTH(4-7) Pro-Gly-Pro.
Another novel approach was the method of administration, although
a much improved resistance towards peptidases had been achieved
through the PGP binding, the relatively small size of the molecule
allowed utilization of the route by retrograde axonal transport
through the N.Olfactorius or N.Trigeminus, by administering
as a solution/drops onto the nasal mucosa or sublingual mucosa.
Adan A.R et al, and Gozes I observed excellent results administering
peptides through the intranasal route and concentrations two
to threefold those achieved by the I.V route have been reported.
The combination of avenues of access to the brain via the retrograde
axonal transport and microcirculation routes contribute towards
the achievement of significant concentrations of the substance
in the brain in a relatively short period (1-3 minutes) and
a significant duration of therapeutic effect (20 hours).