Removal Of Ring Research Articles

A new ultra-wideband, ultra-short monocycle pulse generator with reduced ringing

We introduce a new ultra-wideband (UWB), ultra-short, step recovery diode monocycle pulse generator. This pulse generator uses a simple RC high-pass filter as a differentiator to generate the monocycle pulse directly. The pulse-shaping network employs a resistive circuit to achieve UWB matching and substantial removal of the pulse ringing, and rectifying and switching diodes to further suppress the ringing. An ultra-short monocycle pulse of 300-ps pulse duration, -17-dB ringing level, and good symmetry has been demonstrated. Good agreement between the measured and calculated results was achieved.

Removal of cartilage rings prevents graft stenosis in extended tracheal allotransplantation with omentopexy and immunosuppression: an experimental study

Background One of the serious problems in longer size tracheal transplantation is severe stenosis of the graft, probably caused by an inadequate blood supply. We have previously reported that removal of some cartilage rings of the graft and omentopexy helps to provide sufficient blood flow to the graft mucosal tissue and results in satisfactory survival and non-significant graft stenosis in extended tracheal autotransplantation. However, it is unclear whether this method can be applied to extended tracheal allotransplantation that requires immunosuppression. In this report, we describe midterm results of extended tracheal allotransplantation with the technique. Methods Twenty-four adult mongrel dogs were used. In 18 dogs, a nine-cartilage-ring length of the trachea was allotransplanted when five cartilage rings of the graft were removed, leaving two rings intact at both ends of the graft for simple fixing to the recipient. Two artificial tracheal rings outside the graft and a stent inside the graft were used for maintaining the lumen width. Omentopexy was done for sufficient blood supply to the graft. FK 506 (0.1 mg/kg) was given on each day after the operation in Group A ( n = 10), but was not given at all in Group B ( n = 8). In Group C ( n = 6), a nine-cartilage-ring length of the trachea, without removal of any cartilage ring, was transplanted into the recipient dog and covered with an omental pedicle flap. The same dose of FK 506 as that used in Group A dogs was given to Group C dogs. Results In Group A, 2 dogs died of graft stenosis within 9 weeks after surgery and 1 died of emaciation without tracheal stenosis. Seven dogs (70%) survived until time of killing. Among the 8 dogs in Group B, 6 died of graft stenosis within 9 weeks after surgery, with 1 dying of pneumonia and only 1 (13%) surviving for >1 year until killing. In Group C, all 6 dogs died of graft stenosis within 6 weeks after surgery. Survival at 16 weeks after surgery was 70% in Group A, 13% in Group B and 0% in Group C ( p < 0.01, A vs B and C). No significant graft stenosis was found in 6 dogs and mild stenosis was found in 2 dogs at the time of death or killing in Group A (80%), whereas mild stenosis was found in only 2 dogs in Group B (25%) ( p < 0.05). Mucosal blood flow of the graft in Group A was higher than that in Group C and was the same as that in Group B within 4 weeks after surgery; however, it remained unchanged to ultimately be higher than in Group B at 6 and 8 weeks after surgery. Conclusions Removal of some cartilage rings, omentopexy and immunosuppression improved blood supply to the graft and resulted in good survival and non-significant tracheal stenosis in extended tracheal allotransplantation.

Haemodynamic effects of the bacterial quorum sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, in conscious, normal and endotoxaemic rats.

N-acylhomoserine lactones (AHLs) are small, diffusible signalling molecules, employed by Gram-negative bacteria to coordinate gene expression with cell population density. Recent in vitro findings indicate that AHLs may function as virulence determinants per se, through modification of cytokine production by eukaryotic cells, and by stimulating the relaxation of blood vessels. In the present study, we assessed the influence of AHLs on cardiovascular function in conscious rats, and draw attention to the ability of the N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), a signal molecule produced by P. aeruginosa, to cause marked bradycardia. This bradycardic effect was blocked by atropine and atenolol, and did not occur in vitro. Furthermore, modification of the acyl side chain length resulted in the loss of activity, whereas removal of the homoserine lactone ring, did not. The bradycardic effect of 3-oxo-C12-HSL was also observed in endotoxaemic animals, albeit attenuated. In normal rats, 3-oxo-C12-HSL caused initial mesenteric and hindquarters vasoconstriction, but only slight, and delayed signs of vasodilatation in the renal and mesenteric vascular beds. Furthermore, administration of 3-oxo-C12-HSL (pre-treatment or 2 h post-treatment) together with LPS, did not modify the established regional haemodynamic effects of the LPS, 6 h after the onset of its infusion. Our observations do not provide any clear evidence for an ability of 3-oxo-C12-HSL to modify the haemodynamic responses to LPS infusion. However, they are not inconsistent with the hypothesis that some of the cardiovascular sequelae of bacterial infection may be modulated by an influence of bacterial quorum sensing signalling molecules on the host.

Vitreoretinal alterations following laser in situ keratomileusis: clinical and experimental studies.

The presence of vitreoretinal changes following laser in situ keratomileusis in myopia is evaluated. Clinically, 50 patients (100 eyes) with marked anisometropic myopia, 50 low-myopic eyes (<4.00 D) and 50 high-myopic eyes (>7.00 D) were prospectively evaluated pre- and postoperatively for the presence of newly recognized entoptic phenomena (vitreous floaters, light flashes, or both), and for vitreoretinal changes using indirect depressed fundus examination, a +90 D preset lens, Goldman three-mirror contact lens, and kinetic ultrasound (KU) before and after bilateral LASIK. Patients with previous partial or total posterior vitreous cortex detachment (PVD) were excluded. Experimentally, groups of adult pigs underwent KU, retinal fluorescein angiography (FA), and electroretinography (ERG) before and after applying the microkeratome suction ring for 30 s. Clinically, 8% (4 eyes) had positive perception of postoperative vitreous floaters in the low myopia group, and 32% (16 eyes) in the high myopia group. Postoperative light flashes were noted only in the high myopia group, in 12% of cases. Partial or total posterior vitreous cortex detachment was detected by biomicroscopy in 2% (1 eye) of the low and in 10% (5 eyes) of the high myopia group and by KU in 4% (2 eyes) of the low and in 24% (12 eyes) of the high myopia group. Experimentally, 2 pig eyes out of 12 developed partial PVD by KU, immediately after microkeratome suction ring application. All pig eyes showed significantly diminished ERG amplitudes during and immediately after suction ring application. No FA changes or delays in retinal circulation time were noted during or immediately after removal of the suction ring. Vitreoretinal alterations after LASIK were demonstrated clinically mainly by KU in high myopes. Experimentally, PVD were also demonstrated. Diminished ERG recordings with normal retinal circulation following suction ring application may suggest some transient choroidal circulation abnormalities.

Removal of nail polish and finger rings to prevent surgical infection.

Surgical wound infection may be caused by transfer of bacteria from the hands of the surgical team during operative procedures. Careful surgical scrubbing is therefore performed to reduce the number of bacteria on the skin. The wearing of finger rings and nail polish is thought to reduce the efficacy of the scrub as they are thought to harbour bacteria in microscopic imperfections of nail polish and on the skin beneath finger rings. To assess the effect of removal of finger rings and nail polish by the surgical scrub team, on postoperative wound infection rates. We searched the Cochrane Wounds Group Specialised Trials Register up to November 2000 using the search strategy developed by the Cochrane Wounds Group. We wrote to manufacturers of surgical scrubbing agents for ongoing and unpublished research. Reference lists of articles were searched and relevant journals outside the electronic databases were hand searched. No restriction was placed on literature based on date of publication, language or publication status. Randomised controlled trials evaluating the effect of wearing or removal of finger rings and nail polish by the surgical scrub team on post operative wound infections and number of bacteria on the hands of the surgical scrub team. The abstracts of studies identified were scanned by all reviewers. All abstracts were checked against a checklist to determine whether they fulfilled the inclusion criteria. Full reports of relevant studies were obtained and checked against the checklist by two reviewers. The full reports of all excluded trials were checked by all reviewers independently to ensure appropriate exclusion. We found no randomised controlled trials that compared the wearing of finger rings with the removal of finger rings. We found no trials of nail polish wearing / removal that measured patient outcomes, including surgical infection. We found one small randomised controlled trial which evaluated the effect of nail polish on the number of bacterial colony forming units on the hands after pre-operative hand washing (also called surgical scrubbing). Nurses were allocated to: unpolished nails, freshly applied nail polish (less than two days old), or old nail polish (more than four days old). Both before and after surgical scrubbing, there was no significant difference in the number of bacteria on the hands. There is no evidence of the effect of removing nail polish or finger rings on the rate of surgical wound infection. There is insufficient evidence of the effect of wearing nail polish on the number of bacteria on the skin. However, the one trial making this comparison trial was too small to exclude anything other than a very large difference in the number of bacteria on the skin.

Ring Entrapment of the Finger in a Psychiatric Patient

Ring entrapment of the finger is an uncommon occurrence in our environment and is usually amenable to conservative treatment by removal of the entrapped ring. Gangrene of the affected digit is rare. This is a report of a 57-year-old schizophrenic who developed ulceration, severe oedema and gangrene of the right middle finger following entrapment by a ring like motor spare part. Disarticulation at the metacarpophalangeal joint was necessary. The gangrene was possibly due to a combination of severe oedema, infection or a Raynaud's like phenomenon. (Nig J Surg Res 2001;3:37-40) KEY WORDS: Ring, finger entrapment, gangrene, psychiatric illness

Laser in situ keratomileusis after intracorneal rings: Report of 5 cases

Purpose To examine the results of laser in situ keratomileusis (LASIK) after removal of intracorneal ring (ICR) segments. Setting Active refractive surgery practice. Methods The effect of ICR (0.45 mm) placement, the rapidity of refractive recovery after explantation, and the results of subsequent LASIK were examined in 5 eyes. Results Four eyes developed induced astigmatism after ICR implantation. In 2 of these eyes, retained astigmatism was evident by manifest refraction or corneal topography even after ICR explantation. In 1 eye, the ICR procedure was aborted because of an intraoperative complication. All 5 eyes had subsequent uneventful LASIK. Conclusions Intracorneal rings can induce astigmatism that may be retained even after explantation. Careful wound manipulation may reduce the incidence of this complication. Laser in situ keratomileusis after ICR removal appears to be safe and effective.

Involvement of phylogenetically conserved acidic amino acid residues in catalysis by an oxidative DNA damage enzyme formamidopyrimidine glycosylase.

Formamidopyrimidine glycosylase (Fpg) is an important bacterial base excision repair enzyme, which initiates removal of damaged purines such as the highly mutagenic 8-oxoguanine. Similar to other glycosylase/AP lyases, catalysis by Fpg is known to proceed by a nucleophilic attack by an amino group (the secondary amine of its N-terminal proline) on C1' of the deoxyribose sugar at a damaged base, which results in the departure of the base from the DNA and removal of the sugar ring by beta/delta-elimination. However, in contrast to other enzymes in this class, in which acidic amino acids have been shown to be essential for glycosyl and phosphodiester bond scission, the catalytically essential acidic residues have not been documented for Fpg. Multiple sequence alignments of conserved acidic residues in all known bacterial Fpg-like proteins revealed six conserved glutamic and aspartic acid residues. Site-directed mutagenesis was used to change glutamic and aspartic acid residues to glutamines and asparagines, respectively. While the Asp to Asn mutants had no effect on the incision activity on 8-oxoguanine-containing DNA, several of the substitutions at glutamates reduced Fpg activity on the 8-oxoguanosine DNA, with the E3Q and E174Q mutants being essentially devoid of activity. The AP lyase activity of all of the glutamic acid mutants was slightly reduced as compared to the wild-type enzyme. Sodium borohydride trapping of wild-type Fpg and its E3Q and E174Q mutants on 8-oxoguanosine or AP site containing DNA correlated with the relative activity of the mutants on either of these substrates.

Synthesis and reactivity of a potential carcinogenic metabolite of tamoxifen: 3,4-dihydroxytamoxifen-o-quinone.

Although tamoxifen is approved for the treatment of hormone-dependent breast cancer as well as for the prevention of breast cancer in high-risk women, several studies in animal models have shown that tamoxifen is heptocarcinogenic, and in humans, tamoxifen has been associated with an increased risk of endometrial cancer. One potential mechanism of tamoxifen carcinogenesis could involve metabolism of tamoxifen to 3,4-dihydroxytamoxifen followed by oxidation to a highly reactive o-quinone which has the potential to alkylate and/or oxidize cellular macromolecules in vivo. In the study presented here, we synthesized the 3,4-dihydroxytamoxifen, prepared its o-quinone chemically and enzymatically, and studied the reactivity of the o-quinone with GSH and deoxynucleosides. The E (trans) and Z (cis) isomers of 3,4-dihydroxytamoxifen were synthesized using a concise synthetic pathway (four steps). This approach is based on the McMurry reaction between the key 4-(2-chloroethoxy)-3,4-methylenedioxybenzophenone and propiophenone, followed by selective removal of the methylenedioxy ring of (E, Z)-1-[4-[2-(N,N-dimethylamino)ethoxy]phenyl]-1-(3, 4-methylenedioxyphenyl)-2-phenyl-1-butene with BCl(3). Oxidation of 3,4-dihydroxytamoxifen by activated silver oxide or tyrosinase gave 3,4-dihydroxytamoxifen-o-quinone as a mixture of E and Z isomers. The resulting o-quinone has a half-life of approximately 80 min under physiological conditions. Reaction of the o-quinone with GSH gave two di-GSH conjugates and three mono GSH conjugates. Incubation of 3,4-dihydroxytamoxifen with GSH in the presence of microsomal P450 gave the same GSH conjugates which were also detected in incubations with human breast cancer cells (MCF-7). Reaction of 3, 4-dihydroxytamoxifen-o-quinone with deoxynucleosides gave only thymidine and deoxyguanosine adducts; neither deoxyadenosine nor deoxycytosine adducts were detected. Preliminary studies conducted with human breast cancer cell lines showed that 3, 4-dihydroxytamoxifen exhibited cytotoxic potency similar to that of 4-hydroxytamoxifen and tamoxifen in an estrogen receptor negative (ER(-)) cell line (MDA-MB-231); however, in the ER(+) cell line (MCF-7), the catechol metabolite was about half as toxic as the other two compounds. Finally, in the presence of microsomes and GSH, 4-hydroxytamoxifen gave predominantly quinone methide GSH conjugates as reported in the previous paper in this issue [Fan, P. W., et al. (2000) Chem. Res. Toxicol. 13, XX-XX]. However, in the presence of tyrosinase and GSH, 4-hydroxytamoxifen was primarily converted to o-quinone GSH conjugates. These results suggest that the catechol metabolite of tamoxifen has the potential to cause cytotoxicity in vivo through formation of 3,4-dihydroxytamoxifen-o-quinone.

Symmetric patterns of dislocations in Thomson’s problem

Determination of the classical ground state arrangement of $N$ charges on the surface of a sphere (Thomson's problem) is a challenging numerical task. For special values of $N$ we have obtained using the ring removal method of Toomre, low energy states in Thomson's problem which have icosahedral symmetry where lines of dislocations run between the 12 disclinations which are induced by the spherical geometry into the near triangular lattice which forms on a local scale.

Structural and ionic determinants of 5-nitro-2-(3-phenylprophyl-amino)-benzoic acid block of the CFTR chloride channel.

1. The goals of this study were to identify the structural components required for arylaminobenzoate block of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and to determine the involvement of two positively charged amino acid residues, found within the channel, in drug binding. 2. Wild-type and mutant CFTR chloride channels were expressed in Xenopus oocytes and CFTR currents measured using the two microelectrode voltage clamp. Block of the wild-type CFTR current by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) occurred in a voltage-dependent manner with preferential inhibition of the inward currents (Kd = 166 microM at -90 mV). 3. Removal of the phenyl ring from the aliphatic chain of NPPB, with the compound 2-butylamino-5-nitrobenzoic acid, caused only a small change in CFTR inhibition (Kd = 243 microM), while addition of an extra phenyl ring at this position (5-nitro-2-(3,3-diphenylpropylamino)-benzoic acid) increased drug potency (Kd = 58 microM). In contrast, removal of the benzoate ring (2-amino-4-phenylbutyric acid) or the 5-nitro group (2-(3-phenylpropylamino)-benzoic acid) of NPPB severely limited drug block of the wild-type channel. 4. NPPB inhibition of CFTR currents in oocytes expressing the mutants K335E and R347E also occurred in a voltage-dependent manner. However, the Kds for NPPB block were increased to 371 and 1573 microM, for the K335E and R347E mutants, respectively. 5. NPPB block of the inward wild-type CFTR current was reduced in the presence of 10 mM of the permeant anion SCN-. 6. These studies present the first step in the development of high affinity probes to the CFTR channel.

Removal of cartilage rings of the graft and omentopexy for extended tracheal autotransplantation

Background. One of the serious problems in longer-size tracheal transplantation is infection or severe stenosis of the graft, probably caused by an inadequate blood supply even with omentopexy. For obtaining an appropriate blood supply, we experimentally developed a new technique that included removal of some cartilage rings of the graft and omentopexy. Methods. Twenty-one adult mongrel dogs were used. In group A (n = 11), a nine-cartilage ring length of the trachea in which six of nine rings were removed, leaving one cartilage ring at each end of the graft and another in the center, was autotransplanted with omentopexy. Two artificial tracheal rings outside the graft were used for maintaining the lumen. In group B (n = 10), a nine-cartilage ring length of the trachea was autotransplanted with omentopexy. Results. In group A, all dogs survived until being sacrificed, whereas 5 group B dogs died of graft infection and mediastinitis ( p < 0.05 versus group A). Mucosal blood flow of the graft in group A was normal and higher than in group B ( p < 0.05). Grade of the graft stenosis at death or sacrifice was 14% ± 1% in group A and 58% ± 25% in group B ( p < 0.05). Conclusions. Removal of some cartilage rings improved blood supply to the graft and resulted in satisfactory survival and nonsignificant tracheal stenosis in extended tracheal autotransplantation.

AN IMPROVED METHOD OF RING REMOVAL

A number of techniques exist for the removal of rings from swollen fingers. An improved method is described using ribbon gauze and a paper clip. It is cheap, quick and effective and can be used in the presence of minor lacerations and abrasions.

Synthesis of potent non-imidazole histamine H3-receptor antagonists.

Histamine has been converted into a non-imidazole H3-receptor histamine antagonist by addition of a 4-phenylbutyl group at the N alpha-position followed by removal of the imidazole ring. The resulting compound, N-ethyl-N-(4-phenylbutyl)amine, remarkably has a Ki = 1.3 microM as an H3 antagonist. Using this as a lead compound, a novel series of homologous O and S isosteric tertiary amines was synthesised and structure-activity studies furnished N-(5-phenoxypentyl)pyrrolidine (Ki = 0.18 +/- 0.10 microM, for [3H]histamine release from rat cerebral cortex synaptosomes) which, more importantly, was active in vivo. Substitution of NO2 into the para position of the phenoxy group gave N-(5-p-nitrophenoxypentyl)pyrrolidine, UCL 1972 (Ki = 39 +/- 11 nM), ED50 = 1.1 +/- 0.6 mg/kg per os in mice on brain tele-methylhistamine levels.

Synthesis of methylene isosteres of α- and β-d-galactopyranosyl-l-serine

The BF3·Et2O promoted coupling of tetra-O-benzyl-α-D-galactopyranosyl trichloroacetimidate with a silyl enol ether carrying an oxazolidine ring leads to the α-C-glycosylmethyl ketone (32%, 95% ds) that is converted into the title α-C-glycosyl amino acid by carbonyl oxygen removal (Barton–McCombie) and oxidative cleavage (Jones) of the heterocyclic ring, and into the β-isomer by anomerization and the same two-step sequence.

42-month preliminary follow-up of the silastic ring vertical banded gastroplasty.

The authors review preliminary experience with silastic ring vertical gastroplasty (SRVG). Of 202 patients who underwent SRVG, 191 are more than 3 months postoperation and of these 165 were accessible for review. Pouch volume could not be readily measured. The TA90BN stapler was occasionally difficult to apply exactly at the angle of His. There was one subphrenic abscess, one gastric bleed, and one dehiscence. Vomiting occurred in eight patients who required reoperation: ring removal, three; cholecystectomy, one; conversion to vertical banded gastroplasty, one; conversion to Roux-en-Y gastric bypass, three. There was no mortality. Weight loss has been satisfactory to 42 months. SRVG has been a relatively simple operation, with acceptable morbidity and weight loss thus far.

Imidazoline receptors: Qualitative structure-activity relationships and discovery of tracizoline and benazoline. Two ligands with high affinity and unprecedented selectivity

The observation that all the attempts to characterize imidazoline ( I) receptors have been carried out with non-selective or poorly selective ligands prompted us to undertake research aimed at developing selective ligand(s). In previous work using, as a starting point, cirazoline 1, a potent α 1-adrenergic receptor agonist that also binds to I receptors, we showed that removal of the cyclopropyl ring ( 2) retains high affinity for I 2 receptors while reducing α 1-adrenergic agonist activity. However, it was felt that this residual, albeit modest, α 1-adrenergic agonist activity might diminish the usefulness of compound 2, and we now report on our continuing efforts in this field. Starting from compound 2, we first eliminated the α 1-agonist component by isosteric replacement and then, by means of conformational restrictions on compound 7, succeeded in discovering tracizoline ( 9) and benazoline ( 12). These two new ligands with high affinity (p K i value 8.74 and 9.07, respectively) and unprecedented selectivity with respect to both α 2-( I 2 α 2 7,762 and 18,621) and α 1-( I 2 α 1 2,344 and 2,691) adrenergic receptors, are valuable tools in the study of I receptor structure and function. In addition, the large number of derivatives studied has allowed us to establish congruent qualitative structure-activity relationships and identify some structural elements governing affinity and selectivity.

Supratentorial cavernous angiomas and epileptic seizures: preoperative course and postoperative outcome.

Patients operated on for supratentorial cavernous angiomas were studied to define the incidence and the course of seizures in their clinical history. Electroclinical and neuroradiological data were correlated with the location of cavernomas. The impact of lesionectomy on the outcome of seizures was evaluated. Preoperative clinical data on the history of the seizures, semeiology, incidence, severity, and response to antiepileptic drugs were analyzed. The location of the cavernomas, revealed by magnetic resonance imaging, was correlated with electroencephalographic and clinical data. Postoperative clinical and neuroradiological data were evaluated, with particular consideration to the outcome of the seizures, antiepileptic drug withdrawal, and the completeness of the lesion excision. A higher incidence of severe epilepsy was observed in the patients with mesiotemporal and cortical angiomas. In most of the patients (78.7%), a good concordance between the site of the lesion and the electroclinical data was found. The complete removal of the lesion led to a favorable outcome, with discontinuation of antiepileptic drugs achieved in one-quarter of the patients. A high percentage of patients with cortical cavernomas had epileptic seizures. They often presented with chronic intractable epilepsy (44.7% in our series). In cases of good concordance between the electroclinical data and the location of the angioma, complete lesionectomy led to the disappearance of seizures. Removal of the hemosiderin ring did not correlate with better outcome. Preoperative ictal scalp recordings to assess the topographic relationship between the cavernoma and the epileptic seizures could improve outcome, which suggests different surgical strategies (lesionectomy versus enlarged resection) in patients without a clear-cut concordance between the site of the lesion and the ictal semeiology.

Ring removal in terns caught in Africa ‐ a major problem for population studies

Ring removal in terns caught in Africa ‐ a major problem for population studies

Analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione: structure-activity relationship at N-methyl-D-aspartate receptor glycine sites.

A series of aromatic and azepine ring-modified analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione (HBAD) were synthesized and evaluated as antagonists at NMDA receptor glycine sites. Aromatic ring-modified HBADs were generally prepared via a Schmidt reaction with substituted 2-methoxynaphthalene-1,4-diones followed by demethylation. Electrophilic aromatic substitution of benzazepine 3-methyl ethers gave 7-substituted analogs. The preparation of multiply substituted 2-methoxynaphthalene-1,4-diones was effected via Diels-Alder methodology utilizing substituted butadienes with 2-methoxybenzoquinones followed by aromatization. Structural modifications, such as elimination of the aromatic ring, removal of the 3-hydroxyl group, and transfer of the hydroxyl group from C-3 to C-4, were also studied. An initial evaluation of NMDA antagonism was performed using a [3H]MK801 binding assay. HBADs demonstrating NMDA antagonist activity as indicated by inhibition of [3H]MK801 binding were further evaluated employing a [3H]-5,7-dichlorokynurenic acid (DCKA) glycine site binding assay. Selected HBADs were characterized for functional antagonism of NMDA and AMPA receptors using electrophysiological assays in Xenopus oocytes and cultured rat cortical neurons. Antagonist potency of HBADs showed good correlation between the different assay systems. HBADs substituted at the 8-position possessed the highest potency with the 8-methyl (5), 8-chloro (6), and 8-bromo (7) analogs being the most active. For HBAD 6, the IC50 in [3H]-DCKA binding assays was 0.013 microM and the Kb values for antagonism of NMDA receptors in oocytes (NR1a/2C) and cortical neurons were 0.026 and 0.048 microM, respectively. HBADs also antagonized AMPA-preferring non-NMDA receptors expressed in oocytes but at a lower potency than corresponding inhibition of NMDA receptors. HBADs demonstrating a high potency for NMDA glycine sites showed the highest steady-state selectivity index relative to AMPA receptors. Substitution at the 6-, 7-, and 9-positions generally reduced or eliminated glycine site affinity. Moving the hydroxyl group from C-3 to C-4 reduced receptor affinity, and potency was eliminated by the removal of the aromatic ring or the hydroxyl group. These data indicate that the HBAD series has specific structural requirements for high receptor affinity. With the exception of substitution at C-8, modified HBADs generally have a lower affinity at NMDA receptor glycine sites than the parent compound 3. Mouse maximum electroshock-induced seizure studies show that the three HBADs selected for testing have in vivo potency with the 6,8-dimethyl analog (52) being the most potent (ED50 = 3.9 mg/kg, iv).