Kniga na apstrakti book of abstrcts

Production of monoclonal antibodies against glycoprotein isolated
from human peripheral nerve 
Katerina Brezovska
Faculty of Pharmacy, University Ss. Cyril and Methodius, Vodnjanska 17, Skopje, Macedonia
Supervisor: Carmen Fernandez, Professor
Dept. of Immunology, The Arrhenius Laboratories, Stockholm University
Sera from patients with GBS, following C. jejuni infection, cross-react with several GalGalNAc binding gly-
coproteins isolated from human peripheral nerve and from C. jejuni O:19, which indicates on the possibility of molec-
ular mimicry between these cross-reactive glycoproteins and their potentional role in the development of GBS. The
aim of this study was to produce monoclonal antibodies against glycoprotein isolated from human peripheral nerve,
which cross-react with glycoprotein from C. jejuni O:19, both with electrophoretic mobility between 60 and 70 kDa.
Purification of the glycoproteins with electrophoretic mobility between 60 and 70 kDa, from proteins isolated from
human peripheral nerve and from C. jejuni O:19, was done by preparative SDS-PAGE. BALB/c mouse was immu-
nized with the glycoprotein purified from human peripheral nerve, and screened for production of antibodies against
the immunizing antigen and cross-reactive antigen, glycoprotein purified from C. jejuni O:19, using ELISA.
Splenocytes were fused to myeloma cell line (SP2/0), using polyethylene glycol. Screening of hybridoma cells and
determination of their isotypes was done using ELISA. Supernatants from cultures with positive reactivity to both
immunizing and cross-reactive antigen were tested on Western blot for their binding to total protein isolates and to
purified proteins. Fusion resulted in the generation of 90,10 % (519/576) growth positive cells, and 137 cultures pro-
duced antibodies to immunizing antigen, from which 8 showed positive reactivity to the cross reactive antigen.
Supernatant reacting only immunizing antigen, showed presence of IgG antibodies, subclass IgG1, whereas super-
natant reacting to both antigens, showed presence of IgG and IgM antibodies. Western blot analysis confirmed the
binding of produced antibodies to tested antigens. Further studies are needed for subcloning of positive hybridomas
and purification of monoclonal antibodies against different epitopes on immunizing antigen. These monoclonal anti-
bodies, could be used in further studies for immunochemical and immunohistological characterization of the cross-
reactive glycoproteins present in human peripheral nerve and in Campylobacter jejuni O:19, and help elucidating
their role in the development of GBS.
Macedonian pharmaceutical bulletin 53 (1,2) 23 (2007)
SP - 7
23
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Uptake studies of chitosan-Ca-alginate microparticles 
loaded with 5-FU in human intestinal cell lines
Maja Simonoska Crcarevska
1, 
Katerina Goracinova
1
, Marija Glavas Dodov
1
, Bente Steffansen
2
1
Institute of Pharmaceutical technology, Faculty of Pharmacy, Ss. Cyril and Methodius University, 
Vodnjanska 17, Skopje 1000, Macedonia
2
Department of Pharmaceutics and Analytical chemistry, Faculty of Pharmaceutical sciences,
University of Copenhagen, Universitetsparken 2, Copenhagen 2100, 
Thymidylate synthase (TS), a key enzyme in DNA synthesis, is often overexpreseed in cancer cells. In the
present study, in an order to investigate the efficiency of microparticulated drug delivery systems loaded with 5-FU,
we assessed the sensitivity of folate-dependent thymidylate synthesis to 5-FU standard solution and different formu-
lation of microparticles loaded with 5-FU (Ca-alginate MP`s (CAF); chitosan-Ca-alginate MP`s (CCAF); and chi-
tosan-Ca-alginate MP`s loaded with HPMCP HP 55/ 5-FU in Caco-2 (American Type Culture Collection; LGC, Midde-
lsex, UK), a human colon carcinoma cell line. Micropaticles were produced by one step spray-drying process [1].
Sensitivity was assessed by the degree of inhibition of [methyl-3H] thymidine uptake. Uptake studies were
performed for 24 hours at 37 
0
C in shaking water bath. Caco-2 cells were incubated for 30 min with studied formu-
lations before the addition of 20 
µl of [methyl
-3
H] thymidine standard solution 100 
µCi/ ml. At 6
th
hour, the whole
media was replaced with DMEM supplemented with 10% BSA (500 
µl on the apical side of monolayer, and 1 ml in
receiver chambers). The incubation was continued to 24 hour. The media was aspired with vacuum pump and the reac-
tion was stopped by washing the cells three times with ice-cold HBSS. The cell filters were detached from chambers
and transferred into scintillation vials. Than 2 ml of scintillation cocktail was added and the radioactivity was count-
ed with a liquid scintillation analyzer.
Transport studies of 5-FU from investigated formulations in Caco-2 cells were also done. Transport studies
were performed for 6 hours at 37 
0
C in shaking water bath. At appropriate time intervals (each 30 min during 4 hours
and than at 5 and 6 hour), 100
µl samples from receiver chamber were withdrawn, replaced by 100ml of fresh buffer,
and assayed by HPLC-UV. Analyses were performed on Merck Hitachi HPLC system, equipped with Ellite LaChrom
L-2200 autosampler, L-2130 pump and L-2450 diode array detector. The column used was Waters Spherisorb S5ODS2,
250mm x 4.6mm with S5ODS2 precolumns. The mobile phase was 100% 0.02 M sodium acetate buffer pH 4.0.
Chromatographic conditions set for this method were: flow rate 1 ml/min, column temperature 20 
0
C, UV detection
at 266 nm and injection volume 10 
µl. 
Prepared chitosan-Ca-alginate MP`s loaded with HPMCP HP55/5-FU showed expressive mucoadhesivity
and controlled release properties and significantly lower uptake of [methyl
-3
H] thymidine in Caco-2 cells compared
to standard 5-FU solution. 
Further experiments are towards functionalization of the HPMCP HP 55/5-FU loaded chitosan-Ca-alginateMP,
which will probably attribute to improved MP/cell interaction due to the cytoadhesion of the carrier system [2].
Macedonian pharmaceutical bulletin 53 (1,2) 24 (2007)
SP -8
24
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Chemometric approach for developement, optimization and 
validation of RP RR-HPLC metods for simultaneous determination 
of therapeutically active substances and their related compounds
R. Petkovska
1
, A. Dimitrovska
1
, C. Cornett
2
1
Department of Chemistry, Faculty of Pharmacy, University “Ss.Cyril and Methodius”, 
Vodnjanska 17, 1000 Skopje, R.Macedonia
2
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical sciences, 
University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
The successful analysis of therapeutically active substances in bulk drug or in pharmaceutical formulations
by Reversed-Phase Rapid Resolution High Performance Liquid Chromatography (RP RR-HPLC) relies upon the
investigation, optimization and validation of the applied method. The aim of this investigation was to develop and
validate the RP RR-HPLC metods for separation and simultaneous determination of the therapeutically active sub-
stances and their related compounds specified as impurities that could potentially be present in bulk drug or in phar-
maceutical formulations with the using chemometrics, eg. mathematical and statistical models to design and select
optimal experimental conditions and provide maximum relevant information by analysing experimental data. 
The matrix investigated were laboratory mixtures of five therapeutic active substances with various chemi-
cal properties and polarity of the molecules (lansoprazol, atorvastatin, claritromycin, haloperidol and clopidogrel) and
their related substances. Separation were made on a Zorbax Eclipse XDB C18 Rapid Resolution HT 4.6 mm × 50 mm,
1,8
µ
m particle size column. Experimental designs were used during method optimization and validation (robust-
ness testing). Full factorial 2
3
and full factorial 3
2
designs were used as a screening designs to identify various impor-
tant factors affecting the respective system (mobile phase composition, pH of the mobile phase, column tempera-
ture, flow rate and gradient time) and to develop empirical model of systems. RSM (Response surface methodology)
was applied for determination of the optimum set of relevant experimental chromatographic factors for a separation.
RSM is a graph of system response as a function of one or more factors, and is a visual mean of understanding how
certain factors influence the measurement system. Optimised experimental conditions were applied for RP RR-HPLC
separation of investigated mixtures of therapeutically active substances and their related substances. The methods
were validated statistically for selectivity, linearity, precision, accuracy and robustness. A Central Composite design
was used for robustness testing. For estimation of the system response, selectivity (
α), resolution (R
s
) and a Chroma-
tographic Response Function (CRF) were used as response factors. The CRF is coefficient which characterizes the
quality of the separation in quantitative manner and was used for evaluating the influence of the variation of the
investigated factors on the separation quality of the therapeutically active substances and their impurities in such that
maximum resolution (and all R
s
-values > 2.5) with the minimum assay time was achieved.
The methodology proposed represents an efficient and easily accomplishable approach in resolving the prob-
lems of searching for optimum RP RRHPLC conditions and method validation. Developed methods are capable of
determining the amount and purity of the therapeutically active substances and the quantitative level of impurities
with a total chromatographic purity in a single step.
Macedonian pharmaceutical bulletin 53 (1,2) 25-26 (2007)
SP - 9
25
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Hemometriski pristap pri eksperimentalno dizajnirawe 
na RP RR HPLC metodi za ednovremeno opredeluvawe 
na terapevtski aktivni supstanci i nivni srodni soedinenija
R. Petkovska
1
, A. Dimitrovska
1
, K. Kornet
2
1
Institut za hemija, Farmacevtski fakultet, 
Univerzitet “Sv. Kiril i Metodij”, Vodwanska 17, 1000 Skopje, R.Makedonija
2
Institut za farmacevtska i analiti~ka hemija, Fakultet za farmacevtski nauki,
Univerzitet vo Kopenhagen, Univerzitetparken 2, 2100 Kopenhagen, Danska
Osnovna cel na na{eto istra`uvawe be{e primena na hemometrijata, t.e primena na niza matemati~-
ko - statisti~ki modeli za eksperimentalno dizajnirawe pri razvivawe, optimizacija i validacija na meto-
di za ednovremeno razdvojuvawe i kvantitativno opredeluvawe na terapevtski aktivni supstancii i nivni
one~istuvawata so srodna struktura so primena na reverzno fazna visoko efektivna te~na hromatografi-
ja so mo`nost za brza rezolucija (RP RR HPLC). Vo istra`uvaweto bea vklu~eni pet farmakolo{ki aktivni
supstancii so razli~na hemiska priroda, odnosno polarnost na molekulot (atorvastatin, lansoprazol, halo-
peridol, klaritromicin i klopidogrel) i nivni srodni supstancii koi mo`e da se javat kako one~istuvawa
vo terapevtski aktivnata supstanca ili vo gotov farmacevtski proizvod. Za hromatografsko razdvojuva-
we be{e koristena Eclipse XDB C18 Rapid Resolution HT 4.6 mm h50 mm, 1.8
µm kolona.
Vo procesot na razvivawe na metodite bea primeneti potpoln faktorski 2
3
dizajn i potpoln faktor-
ski 3
2
dizajn. Primenata na ovie eksperimentalni dizajni be{e so cel da se utvrdi: koi od ispituvanite eks-
perimentalni faktori (sostav na mobilna faza, pH na mobilna faza, promena na sostav na mobilna faza vo
tek na gradientno eluirawe, vreme na gradientno eluirawe, protok na mobilna faza i temperatura na kolona)
imaat najgolemo vlijanie na analiti~kiot odgovor, nivoto na me|ufaktorski interakcii kako i konstrui-
rawe na empiriski model na eksperimentalniot sistem. Za procenka na zna~ajnosta na vlijanieto od ispi-
tuvanite eksperimentalni faktori be{e koristena vrednosta na rezolucijata (R
s
) me|u dobienite pikovi.
Optimizacijata na vrednostite na predhodno utvrdenite zna~ajni eksperimentalni faktori be{e
izvr{ena so primena na dizajn na povr{ina na odgovor (RSM). Ovoj dizajn dava mo`nost za konstruirawe
na dijagram vrz osnova na koj e vozmo`na to~na procenka kako na optimalnite vrednosti na zna~ajnite eks-
perimentalni faktori, taka i na nivoto na me|ufaktorski interakcii.
Razvienite metodi bea validirani preku opredeluvawe na linearnost, preciznost, to~nost i robust-
nost. Za opredeluvawe na robustnosta na metodite be{e primenet t.n. Central Composite Design. Procenkata
na odgovorot na eksperimentalniot sistem vo tek na utvrduvaweto na robustnosta na metodite be{e vr{ena
vrz osnova na vrednostite za selektivnost (
α) i rezolucija (R
s
) me|u pikovite koi vrednosti bea koristeni
za presmetuvawe na funkcija na hromatografski odgovor (CRF). Funkcijata na hromatografski odgovor ovoz-
mo`i procenka na kvalitetot na hromatografskoto odvojuvawe na kvantitativen na~in, taka {to be{e post-
ignata vrednost na najgolema mo`na rezolucija (vrednosti za R
s
> 2.5) za najmalo mo`no vreme na odvojuvawe.
Primenetata metodologija ovozmo`i brz, ednostaven i to~en proces na razvivawe, optimizacija i
validacija na metodite. Razvienite metodi davaat mo`nost za ednovremeno kvantitativno opredeluvawe i
utvrduvawe na ~istotata na ispituvanite terapevtski aktivni supstancii.
Macedonian pharmaceutical bulletin 53 (1,2) 25-26 (2007)
SP - 9
26
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Does Cerebral Cortical Brain Slices from PTZ-kindled mice 
provide a more predictive screening model for antiepileptic drugs?
Zoran Sterjev
1
, Henrik T Vestergaard
2,
Suzanne L. Hansen
2
1
Institute of Pharmaceutical Chemistry, Faculty of Pharmacy – University Sts Cyril and Methodius,
Vodnjanska 17, 1000 Skopje, R.Macccedonia,
2
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, 
University of C openhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
Epilepsy is one of the most common serious brain disorders. For the past several decades, epilepsy has been
treated with only a handful of drugs. Since 1993, several novel antiepileptic drugs have been introduced in an attempt
to overcome the limitations of traditional therapy i.e pharmacoresistance and lack of antiepileptogenic drugs.
Pharmacoresistant epilepsy is a major health problem, associated with increased morbidity and mortality, and account-
ing for much of the economic burden of epilepsy. Current antiepileptic drugs (AEDs) do not seem to prevent or to
reverse drug resistance in 20-25% of patients, Consequently, there remains a significant need for development of
new compounds with antiepileptogenic properties. The various animal models for epilepsy that are currently used
in the search for new AEDs are models which have been used to identify traditional antiepileptic drugs. This may
hamper the identification of compounds with new mechanisms of action. 
The cortical wedge preparation is a model of epileptiform activity and has been used to study the effects of
several antiepileptic drugs. However, the predictability of this model has been questioned because a number of false
positive and false negative compounds have been identified. For example: The NMDA receptor antagonist MK-801
has been shown to inhibit spontaneous epileptiform discharges in the cortical wedge model [1] but was without anti-
convulsant effect in amygdale-kindled rats [2]. We therefore set out to investigate whether the use of PTZ-kindled
mice would make the cortical wedge model more predictive.
We have used brain slices from PTZ–kindled, saline-treated and naive mice to study the pharmacological
profile of carbamazapine (CBZ), phenobarbital (PB) and citalopram (CIT) in the cortical wedge model. Four week
old male NMRI mice were injected with 43 mg/kg pentylentetrazole (PTZ), saline or handled as injected ”naïve” 3
times a week for 4 weeks. Only the PTZ – injected mice that were kindled, i.e experiencing two out of three clonic
convulsions following injection, were used for in vitro experiments. Mice were decapitated and the brain rapidly
removed and placed in ice cold O
2
/CO
2
(95%/5%) saturated artificial cerebrospinal fluid (aCSF). Coronal slices (400
?m) were cut and separated using a vibratome, cortical tissue was then separated from the sub-cortical structures.
Approximately 1.5 mm thick slices, was cut from each hemisphere and the striatal tissue was trimmed off. The wedge
was mounted across the slot between two-wall separated compartment baths. In each compartment Ag/AgCl elec-
trodes were placed in contact with dishcloth tissue providing, when wetted, electrical contact to the wedge. PB was
tested within the concentration range of 30-3000 µM, CBZ 10-200 µM and CIT 0,1 – 300 µM. Our preliminary
results show that PB and CBZ concentration-dependently reduced the frequency of the SEDs and the total depolar-
izing shift whereas CIT had almost no effect on frequency of the SEDs or a total depolarizing shift. We will present
our complete findings on the congress.
Macedonian pharmaceutical bulletin 53 (1,2) 27-28 (2007)
SP - 10
27
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Dali cerebralno kortikalnite mozo~ni preseci dobieni 
od eksperimentalni gluvci prethodno tretirani 
so pentatetrazol mo`at da ovozmo`at podobar 
predviduva~ki model za antiepilepti~nite lekovi?
Zoran Sterjev
1
, Henrik T Vestergaard
2
, 
Suzanne L. Hansen
2
1
Institut z a Farmacevtska hemija, Farmacevtski fakultet, 
Univerzitet Sv. Kiril i Metodij, Vodwanska 17, 1000 Skopje, R.Makedonija;
2
Institut za Farmakologija i Farmakoterapija, Fakultet za farmacevtski nauki, 
Kopenhagen Univerzitet, Univerzitetparken 2, 2100 Kopenhagen, Danska
Epilepsijata e edno od najserioznite mozo~ni zaboluvawa. Vo izminatite nekolku dekadi, epilep-
sijata bila tretirana samo so ograni~en broj na lekovi. Posle 1993 godina, promovirani se nekolku novi
antiepilepti~ni lekovi so so osnovna cel nadminuvawe na ograni~uvawata na dotoga{nata terapija.
Farmakorezistentnata epilepsija e glaven medicinski problem koj e asociran so zgolemena stapka na nei-
zle~ivost i smrtnost, {to od druga strana e proprateno i so zgolemeni tro{ocite povrzani so epilepsi-
jata. Postojanite antiepilepti~ni lekovi (AEL) ne mo`at da ja preveniraat ili povratat terapevtska-
ta neefikasnost koja se zabele`uva kaj 20-25% od pacientite. Kako rezultat na toa se nametnuva zna~ajna
potreba od razvoj na novi lekovi so antiepilepti~ni karakteristiki. Razli~ni `ivotinski modeli koj
{to se primenuvaat za istra`uvawata povrzani so AEL-vi se modeli koj se koristat za identifikacija
na tradicionalnite antiepilepti~ni lekovi. Toa mo`e da pretstavuva pre~ka vo identifikacijata na
lekoviti komponenti koi se karakteriziraat so nov mehanizam na deluvawe.
Modelot na Cortical wedge se koristi za prou~uvawe na efektite na nekolku antiepilepti~ni lekovi.
Predvidlivosta na ovoj model e ~esto osporuvana kako rezultat na dobienite diskutabilni pozitivni i
negativni rezultati. Na primer: NMDA receptorniot antagonist MK-801 ja inhibiral spontanata epilep-
togena aktivnost koga bil ispituvan so Cortical wedge modelot no ne poka`uval antikonvulzivni efekti
koga se koristel model so staorci predhono tretirani so amygdal. Poa|aj}i od toa na{ata osnovna cel
be{e da vidime daliu primenata na eksperimentalni gluv~iwa koi prethodno se tretirani so pentate-
trazol kaj Cortical wedge modelot, mo`e da go napravi ovoj model pove}e prediktiven.
Za taa cel koristeni se preseci od cortex dobieni od PTZ - tretirani gluv~iwa, i kontrolna grupa
(gluv~iwatretirani so iziolo{ki rastvor i netretirana grupa na gluv~iwa vrz koi be{e ispituvan far-
makolo{kiot profil na lekovite karbamazepin (CBZ), phenobarbital (PB) i citalopram (CIT). Eksperimentalni
ma{ki NMRI gluv~iwa bea tretirani so 43mg/kg pentatetrazol i fiziolo{ki rastvor 3 pati vo tek na 4
nedeli. Od grupata na PTZ tretirani gluv~iwa za ponatamo{miot eksperiment bea koristeni samo
gluv~iwata koi pojavija konvulzii minimum 2 pati vo tek na tri serii na injektirawe. Eksperimentalnite
gluv~iwata bea umrtvuvani i mozokot brzo otstranet i prenesen vo laden cerebrospinalen rastvor prethod-
no saturiran so me{avina od O
2
/CO
2
(95%/5%). Koronalnite preseci se dobivaat so presekuvawe na kor-
tikalnoto tkivo so pomo{ na elektri~en vibratoren no`.
Tenki preseci od 1.5 mm otse~eni od sekoja hemisfera se postavuvaat pome|u dve kadi~ki me|useb-
no odvoeni so pregraden yid na koi se postavuva Ag/AgCl elektrodi koi se vo kontakt so pdlogata na koja
e postaven presekot. PHT be{e ispituvan vo koncentracionen interval od 30-3000 µM, CBZ 10-200 µM i
CIT 0,1 - 300 µM. Kompletnite rezultati }e bidat prezentirani na kongresot.
Macedonian pharmaceutical bulletin 53 (1,2) 27-28 (2007)
SP - 10
28
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Structural based drug research on ionotropic Glutamate receptors
Zorica Serafimoska
1
,
Ewa Szymanska
1
,
Darryl Pickering
2
,
Karla Frydenvang
2
, 
Jette Kastrup
1
, Tommy N. Johansen
1
1
Departments of Medicinal Chemistry and  
2
Pharmacology and Pharmacotherapy, 
Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark. 
Ionotropic glutamate receptors (iGluRs) constitute a family of ligand gated ion channels subdivided in three
classes NMDA, AMPA and KA receptors according to the agonist that selectively activates them. They play an
important role in mediating fast synaptic transmission in the central nervous system and are considered to be involved
in certain neurological disorders and degenerative brain diseases that are currently without any satisfactory thera-
peutic treatment. AMPA receptors are tetrameric assemblies of GluR1-4 subunits, whereas KA receptors assemble
of GluR5-7 and KA1,2 subunits. In order to identify subtype selective antagonists that discriminate between homo-
meric AMPA and KA receptors a serial of compounds have been synthesized based on the published X-ray struc-
ture of the competitive antagonist (S)-ATPO co-crystallized with the ligand-binding domain of GluR2 (S1S2).
(S)-ATPO
EL-7    
The present project has been focused on molecular modeling, X-ray crystallography and radioligand binding
studies using cloned receptors in order to identify structural determinants for subtype selectivity of competitive
iGluRs antagonists. 
Based on molecular modeling and pharmacological binding data a group of compounds was selected for co-
crystallization with the ligand binding domain of GluR2 (S1S2). Suitable crystals for X-ray crystallography were
obtained for EL-7 which is a competitive antagonist slightly more potent then ATPO. The structure was determined
with a resolution of 1.9 Å. The structure provides interesting structural information on the water mediated interactions
between the ligand and one particular amino acid residue of the ligand binding domain; i.e. Tyr702 which is the only
non-conserved amino acid residue of the ligand binding domain among the four AMPA receptor subunits. Another
interesting finding is the domain closure which is in range between 6.9°-9.1°. This range of domain closure is close
to be in between what has been observed previously for antagonists (ATPO: 2.5°-5.1°) and partial agonist (KA: 13°).
A series of 78 compounds synthesized based on ATPO structure was tested in radioligand binding studies on
recombinant GluR1,3,5,6 and 7 receptors. Based on the results, detailed structure-activity relationship (SAR) could
be established. Among the series of compounds, GluR1,3-prefering as well as GluR5-prefering compounds were
identified. Interestingly, a few compounds with selective affinity for GluR7 was observed. 
The established SAR may prove useful as a good starting point for the synthesis of compounds with a more
selective receptor profile.
Macedonian pharmaceutical bulletin 53 (1,2) 29-30 (2007)
SP - 11
29
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION
COOH
HO OC
H
2
N
Cl
NO
2