Biomedical subjects

C Y Hong

Publications and source records attributed to C Y Hong.

At least 55 records · Page 3Linked to original sources

PubMed1999

Effect of magnolol on in vitro mitochondrial lipid peroxidation and isolated cold-preserved warm-reperfused rat livers.

BACKGROUND/AIM: A mechanism suggested to cause injury to preserved organs is the generation of oxygen free radicals. Lipid peroxidation is one of the biological damages caused by oxygen free radicals. It is our aim to investigate whether magnolol, a strong antioxidant, suppresses the generation of oxygen free radicals and improves the viability of cold-preserved warm-reperfused rat livers. MATERIALS AND METHODS: In vitro lipid peroxidation was induced in rat hepatic mitochondria with ADP and FeSO4. The inhibitory effect of magnolol on lipid peroxidation was measured with oxygen consumption and malondialdehyde (MDA) formation. Subsequently, we preserved and reperfused rat livers in preservation solutions that contained magnolol. The hepatic enzymes and liver MDA were measured to assess the protective effect of magnolol on isolated rat livers. RESULTS: In rat hepatic mitochondria, magnolol was 470 times more potent than alpha-tocopherol in inhibiting oxygen consumption and 340 times more potent than alpha-tocopherol in inhibiting MDA formation. Addition of magnolol to Ringer's lactate solution had a protective effect, in terms of MDA formation and leakage of hepatic enzymes, on warm-reperfused but not cold-stored liver tissue. Addition of magnolol to University of Wisconsin (UW) solution, a widely used preservation solution, did not modify the effect of this solution on isolated liver tissues. CONCLUSIONS: We conclude that magnolol is an effective antioxidant and suppresses lipid peroxidation in rat liver mitochondria and can be used as a rinsing solution in protecting transplanted organs from lipid peroxidation during reperfusion, especially for those organs not preserved with UW solution.

Animals↗

PubMed1999

Pharmacological characterization of LB50016, N-(4-amino)butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist.

LB50016 was characterized as a selective and potent 5-HT1A receptor agonist and evaluate its anxiolytic and antidepressant activities. It shows high affinity for 5-HT1A receptor, moderate affinity for alpha 2 adrenergic and 5-HT2A receptors and no significant affinity for other receptors tested. Hypothermia and increased serum corticosterone level were observed in LB50016-treated rats, which are mediated mostly by post synaptic 5-HT1A receptor activation. In the mouse forced swim model for depression, LB50016-elicited dose-dependent reductions in immobility time, showing ED50 of approximately 3 mg/kg i.p., which was blocked by pretreatment of NAN-190, 5-HT1A antagonist. In face-to-face test for anxiolytic activity in mice, estimated ED50 was 2 mg/kg, i.p. In isolation-induced aggression test with mice, fifty-fold increases in latency to attack were observed at 30 min and last up to 4 h after LB50016 treatment (3 mg/kg, i.p.). Taken together, LB50016-induced pharmacological activities are mediated by activation of 5-HT1A receptors, offering an effective therapeutic candidate in the management of anxiety and depression in humans.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1999

Trilinolein potentiates the pro-aggregating effect of phorbol-12-myristate 13-acetate in human polymorphonuclear leukocytes.

Trilinolein, a triacylglycerol with linoleic acid as the only type of fatty acid residue in all three of the glycerol esterified positions, was recently reported to have an antiplatelet effect, mediated through stimulating nitric oxide and cyclic guanosine monophosphate (GMP) formation. In our study, trilinolein induced aggregation of human polymorphonuclear neutrophils (PMNs) and, pretreatment with 0.1 nM trilinolein enhanced phorbol-12-myristate 13-acetate (PMA) induced aggregation. Further investigation showed that trilinolein at concentrations ranging from 0.1 nM to 10 microM increased cyclic GMP formation after 10 min of incubation with PMNs. Pretreatment of trilinolein with 10 microM d-sphingosine, before being incubated with PMNs, attenuated the stimulatory effect of trilinolein on cyclic GMP formation, and pretreatment of 10 microM d-sphingosine also attenuated the aggregation induced by PMA and trilinolein. We conclude that trilinolein can induce the aggregation of human PMNs, and enhance the aggregation induced by PMA.

Cell Aggregation↗

PubMed1999

Somatic electrical nerve stimulation regulates the motility of sphincter of Oddi in rabbits and cats: evidence for a somatovisceral reflex mediated by cholecystokinin.

Cholecystokinin (CCK) plays an important role in regulating the biliary motility in herbivorous and carnivorous animals. Little is known about how the motility of the sphincter of Oddi (SO) is regulated through a somatic stimulation. It was our aim to test the hypothesis that somatic electrical nerve stimulation (SENS) affects SO motility in animals with different types of SO through CCK-related mechanisms. The activity of SO in anesthetized rabbits and cats was measured by using a continuously perfused open-tip manometric method. SENS was brought about by applying an electric current (2/15 Hz alternatively, 20 min) to two needles positioned near spinal nerves in the 6th and 7th intercostal space in the right midclavicular line. The SO motility before and X min after the start of SENS, designated as pre-SENS and SENS-X respectively, were recorded and saved in a computer equipped with off-line analysis software. The SO activity in rabbits, in terms of phasic contraction pressure and duration of summation peak during SENS were significantly higher than that before SENS. The phasic contraction pressure of pre-SENS, SENS-10, and SENS-16 were 6.83 +/- 0.39 mm Hg, 9.23 +/- 0.83 mm Hg and 10.46 +/- 0.81 mm Hg, respectively (P < 0.03, N = 13). The duration of summation peak in pre-SENS, SENS-10, and SENS-16 were 7.26 +/- 0.41 sec, 10.22 +/- 0.46 sec, and 13.49 +/- 2.31 sec, respectively (P < 0.05, N = 13). The SENS-induced SO hyperactivity was not inhibited by pretreatment with atropine, propranolol, phentolamine, or naloxone, but was blocked by pretreatment with the CCK receptor antagonist, proglumide, and by injection of anti-CCK-8 antibody during SENS in a dose-dependent manner. In contrast, SENS induced an inhibitory SO response in cats. However, in both circumstances, an obvious elevation of plasma CCK level determined by radioimmunoassay was noted after SENS. We conclude that SENS causes secretion of CCK, which in turn affects biliary tract motility in animals with different types of SO. This provides an easily applicable method for those patients who have hyperactive SO function.

Animals↗

PubMed1999

Acute hemodynamic effects of tetramethylpyrazine and tetrandrine on cirrhotic rats.

The hemodynamic effects of tetramethylpyrazine (TMP) and tetrandrine (TET), both alkaloids isolated from Chinese herbs Ligusticum wallichii Franch and Stephania tetrandra S. Moore, respectively, were assessed in anesthetized cirrhotic rats. TMP induced dose-dependent decreases of portal venous pressure (P.V.P.) and mean arterial pressure (M.A.P.) after intravenous infusion. The maximum percentage reduction of P.V.P. after TMP was 3.6 +/- 0.8%, 6.8 +/- 0.5%, and 17.8 +/- 0.6% of baseline, respectively, for the dosages given (3.0, 9.9 and 30.0 mg/kg). Similarly, TET induced dose-dependent decreases of P.V.P. and M.A.P. The maximum percentage reduction of P.V.P. after TET was 5.4 +/- 1.0%, 9.2 +/- 0.8%, and 23.7 +/- 1.2% of baseline, respectively, for the dosages given (2.0, 6.6 and 20.0 mg/kg). Total peripheral resistance was also reduced by TMP as well as TET. Our results showed that TMP and TET induced P.V.P. reduction in cirrhotic rats, together with reduction in M.A.P. and total peripheral resistance.

Alkaloids↗

PubMed1999

Haemodynamic effects of chronic tetramethylpyrazine administration on portal hypertensive rats.

OBJECTIVE: The purpose of this study was to investigate the therapeutic effects of tetramethylpyrazine, an alkaloid isolated from a Chinese herb Ligusticum wallichii Franch, on portal hypertensive rats. METHODS: There were three groups of animals: partial portal vein ligated (PVL) rats, bile duct ligated (BDL) rats and sham-operated (Sham) rats. Each rat in every group was given only one of three treatment regimens: tetramethylpyrazine 30 or 50 mg/kg/12 h, or vehicle (0.2 N HCl, 0.7 ml/12 h). There were seven rats allocated to each regimen, with a total of 63 rats studied. Tetramethylpyrazine or vehicle was given via gastric gavage every 12 h for 8 days, starting just after PVL or 3 weeks after BDL, and haemodynamic parameters were measured thereafter. RESULTS: Both PVL and BDL rats exhibited portal hypertensive and hyperdynamic state as compared with Sham rats. Eight-day tetramethylpyrazine treatment induced dose-dependent reductions of portal venous pressure (PVP), mean arterial pressure (MAP), and total peripheral resistance (TPR) in both PVL and BDL rats. Tetramethylpyrazine at 30 and 50 mg/kg/12 h induced PVP reduction by 10.2 and 16.1% in PVL rats, and 10.5 and 14.8% in BDL rats, respectively, as compared with the vehicle group. There were no significant changes of cardiac index or heart rate (HR) after tetramethylpyrazine treatment in either PVL or BDL rats. In the Sham rats, tetramethylpyrazine did not significantly change PVP, MAP, HR or TPR, despite a tendency of reduction. CONCLUSION: Our results showed that 8-day treatment of tetramethylpyrazine induced reductions of both portal venous and systemic arterial pressure in portal hypertensive rats with and without cirrhosis. Overall, the therapeutic effects are neither outstandingly efficacious nor altogether beneficial.

Animals↗

PubMed1999

Portal hypotensive effects of combined terlipressin and DL-028, a synthetic alpha 1 adrenoceptor antagonist administration on anesthetized portal hypertensive rats.

AIMS/BACKGROUND: The purpose of this study was to investigate the therapeutic effects of terlipressin, alone or in combination with DL-028, a synthetic alpha 1-adrenoceptor antagonist on anesthetized portal hypertensive rats. METHODS: Portal hypertension was induced by either partial portal vein ligation (PVL) or bile duct ligation (BDL) in Sprague-Dawley rats. Each portal hypertensive rat received only one of the two regimens: vehicle plus terlipressin or DL-028 plus terlipressin. Terlipressin dosage was 0.017 mg/kg/min infused for 3 min, while vehicle or DL-028 (0.50 microgram/kg/min) was continuously infused for 40 min, starting 10 min before terlipressin infusion. RESULTS: In PVL rats, infusions of vehicle plus terlipressin induced significant, maximum reduction of portal venous pressure (PVP, -11.0 +/- 1.8%) and prominent elevation of mean arterial pressure (MAP, 50.3 +/- 9.0%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (-17.5 +/- 2.8%) and MAP elevation (39.8 +/- 7.4%). In BDL rats, infusion of vehicle plus terlipressin also induced significant, maximum reduction of PVP (-6.8 +/- 2.1%) and prominent elevation of MAP (61.4 +/- 7.8%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (-17.9 +/- 2.2%) and MAP elevation (47.9 +/- 7.4%). Compared to vehicle plus terlipressin, DL-028 significantly enhanced portal hypotensive effects of and attenuated systemic pressor effects of terlipressin in both PVL and BDL rats. CONCLUSIONS: Our results suggest that terlipressin, alone or in combination with DL-028, induced portal hypotensive effects in portal hypertensive rats. The combination of terlipressin with DL-028 was beneficial in enhancing the portal hypotensive effects and ameliorating the systemic pressor effects of terlipressin.

Adrenergic alpha-Antagonists↗

PubMed1999

Infrequent p53 mutations in patients with areca quid chewing-associated oral squamous cell carcinomas in Taiwan.

Mutations in the conserved regions (exons 5-9) of the p53 gene were investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing analyses. P53 mutations were detected in 2 of 37 (5.4%) oral SCC cases. One tumor sample (case 23) showed a mis-sense point mutation at codon 177, changing CCC to CTC, which resulted in a substitution of proline to leucine in the p53 protein. The other tumor (case 33) had a point mutation at codon 266, changing GGA to AGA and causing a substitution of glycine to arginine in the p53 protein. These two patients with p53 mutations did not have an areca quid chewing habit. These results suggest that mutations in the p53 gene may not play a role in the pathogenesis of human oral SCCs in Taiwan. Recently, we have shown that positive p53 staining was observed in 47 of 81 (58%) cases of oral SCC. The discrepancies between positive p53 protein staining and the low prevalence of p53 mutation in oral SCCs indicate that other mechanism(s) are involved in p53 overexpression.

Adult↗

PubMed1999

Effects of exonuclease activity and nucleotide selectivity of the herpes simplex virus DNA polymerase on the fidelity of DNA replication in vivo.

A mutagenesis system was developed for the in vivo study of the fidelity of DNA replication mediated by wild-type herpes simplex virus type 1 (HSV-1) strain KOS and its polymerase (Pol) mutant derivatives PAAr5, Y7, and YD12. The pHOS1 shuttle plasmid, which contained the SupF mutagenesis marker gene and the HSV oris sequence, was used for analysis of the mutation frequency and the mutation spectrum. All three Pol mutants induced significant increases in the mutation frequencies of the target gene, despite the fact that PAAr5 was previously shown to have an antimutator phenotype by the thymidine kinase mutagenesis assay (J. D. Hall, D. M. Coen, B. L. Fisher, M. Weisslitz, S. Randall, R. E. Almy, P. Gelep, and P. A. Schaffer, Virology 132:26-37, 1984; C. B. C. Hwang and J.-H. Chen, Gene 152:191-193, 1995). Altered spectra of mutated target genes induced by these three mutants were also observed. The relative frequencies of both deletion and complex mutations found in mutants induced by exonuclease-proficient Pols were significantly higher than those induced by exonuclease-deficient Pols. On the other hand, the exonuclease-deficient Pols induced significant increases in the frequency of base substitutions, which comprised predominantly G. C-to-T. A transversions, as well as mutations at additional hot spots. These results suggest that the HSV-1 DNA Pol can incorporate purine-purine or pyrimidine-pyrimidine mispaired bases which may be preferentially proofread by its intrinsic exonuclease activity. Furthermore, the effects of the sequence context of the target gene and the assay method should also be considered carefully in any analysis of replication fidelity.

Animals↗

PubMed1999

Antiarrhythmic effect of magnolol and honokiol during acute phase of coronary occlusion in anesthetized rats: influence of L-NAME and aspirin.

This study was designed to evaluate the in vivo effect of magnolol and honokiol on the acute phase of coronary ligation in the presence of nitric oxide inhibitor (L-NAME) or cyclooxygenase inhibitor (aspirin). After Sprague-Dawley rats were anesthetized with urethane, the changes of ventricular arrhythmia induced by coronary ligation for 30 min were determined with or without pretreatment with study medications. The incidence and duration of ventricular arrhythmia were significantly reduced after intravenous pretreatment (15 min before coronary ligation) with 10(-7) g/kg magnolol or 10(-7) g/kg honokiol. However, the antiarrhythmic effect of magnolol or honokiol could be abolished with the pretreatment of 1 mg/kg L-NAME, but not with pretreatment of 100 mg/kg aspirin. The abolishment of the myocardial beneficial effect of magnolol and honokiol by L-NAME, instead of aspirin, suggests an involvement of an increased nitric oxide synthesis in the protection offered by magnolol and honokiol against arrhythmia during myocardial ischemia.

Anesthesia↗

PubMed1999

Effects of dipyridamole, nitroglycerin, and nitroprusside on coronary vascular resistance in rabbits: measurement with pulsed Doppler velocimetry.

Dipyridamole, nitroglycerin, and nitroprusside are all effective vasodilators. However, few studies have compared their in vivo coronary vasodilatation effects. The purpose of this study was to compare the effects of these agents on coronary blood flow velocity and vascular resistance in anesthetized, open-chest rabbits. Male New Zealand white rabbits were anesthetized, and a 3-mm, suction-type, pulsed Doppler velocimeter probe was applied to the proximal part of the left anterior descending coronary artery after median sternotomy. The rabbits received infusion of various doses of dipyridamole (0.1 mg/kg, n = 5; 1 mg/kg, n = 5; 10 mg/kg, n = 9), nitroglycerin (0.01 mg/kg, n = 8; 0.1 mg/kg, n = 5; 1 mg/kg, n = 5; 10 mg/kg, n = 7), or nitroprusside (0.01 mg/kg, n = 5; 0.1 mg/kg, n = 5; 1 mg/kg, n = 5). The percent changes in coronary blood flow velocity and coronary vascular resistance were measured. All three vasodilators increased coronary blood flow velocity significantly and decreased coronary vascular resistance dose-dependently. The dose-response curves of dipyridamole, nitroglycerin, and nitroprusside were significantly different from one another (p < 0.01). Dipyridamole at a dose of 10 mg/kg produced the greatest increase in coronary blood flow velocity and the greatest reduction in coronary vascular resistance in anesthetized, open-chest rabbits.

Analysis of Variance↗

PubMed1999

Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats.

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg x kg(-1) x min(-1) for 3 min) or TMP (10 mg x kg(-1) x min(-1) for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0+/-1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3+/-8.1%) as well as total peripheral resistance (TPR, 113+/-11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3+/-1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3+/-0.4%) and CI (-9.9+/-1.2%) and significant elevation of MAP (31.3+/-2.5%) and TPR (46.0+/-4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8+/-1.7%) but an increase in MAP (57.1+/-2.2%) and TPR (101+/-6%) from baseline, and there also was a cardiodepressant response (CI, -21.4+/-2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9+/-1.4%) and CI (-11.9+/-2.1%), but an increase in MAP (36.2+/-2.5%) and TPR (55.0+/-5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.

Animals↗

PubMed1998

Benzylamine-based selective and orally bioavailable inhibitors of thrombin.

A series of p-aminomethylphenylalanine derivatives were investigated as novel thrombin inhibitors. This study led to potent inhibitors of thrombin (Ki up to 3.3 nM) that are trypsin-selective, highly orally bioavailable in rats, and highly permeable across Caco-2 cells. The P1 benzylamine binding mode in the thrombin active site was identified by X-ray crystallographic analysis.

Animals↗

PubMed1998

Solid phase synthesis of benzylamine-derived sulfonamide library.

Using solid phase synthesis, a library has been constructed of benzylamine-derived sulfonamides which have strong inhibitory activity against the blood coagulant thrombin. The library compounds were obtained in good yield and high purity; four of these thrombin inhibitors showed nanomolar potency (Ki 600-10 nM).

Anticoagulants↗

PubMed1998

Methyloxime-substituted aminopyrrolidine: a new surrogate for 7-basic group of quinolone.

Novel fluoroquinolones containing oxime functionalized aminopyrrolidines have been synthesized. They were found to possess potent antibacterial activities against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Among these compounds, LB20277 (compound 12) showed the most favorable in vivo efficacy and pharmacokinetic profile in animals. Based on these promising results, LB20277 was selected as a candidate for further evaluation.

Animals↗

PubMed1998

Local somatothermal stimulation inhibits the motility of sphincter of Oddi in cats, rabbits and humans through nitrergic neural release of nitric oxide.

To examine whether and how local somatothermal stimulation inhibits the function of the sphincter of Oddi (SO) in humans and in animals with different types of SO, we measured the activity of SO in anesthetized cats and rabbits by using continuously perfused open-tip manometric methods. Local somatothermal stimulation was achieved by applying an electroheating rod 0.5 cm away from the skin area near the right subcostal region. A heating pad was applied to the corresponding area in patients undergoing endoscopic retrograde cholangiopancreatography and biliary manometry. The motility of the biliary tract in cats, in terms of gall bladder pressure, tonic and phasic contraction pressure and frequency of SO before and during local heat were significantly different, respectively. The local heat-induced SO relaxation was not inhibited by pretreatment with atropine, propranolol, phentolamine or anti-cholecystokinin-octapeptide, but was almost completely blocked by infiltration of local anesthetics. Pretreatment with a nitric oxide synthesis inhibitor also blocked the relaxation, which was reversed by pretreatment with L-arginine, but not by D-arginine. The inhibition of SO motility by local heat in rabbits was also blocked by pretreatment with L-NAME, and this blockade was reversed by L-arginine. Application of local heat on patients demonstrated obvious inhibitory SO responses. We conclude that local somatothermal stimulation inhibits the SO motility in animals with different types of SO through the activation of heat-sensitive neural release of nitric oxide. This procedure may represent a simplified approach for the treatment of diseases with hypofunction of the L-arginine/NO pathway.

Animals↗

PubMed1998

Vascular hyporeactivity persists despite increased contractility after long-term administration of isosorbide dinitrate in portal hypertensive rats.

BACKGROUND/AIMS: Portal hypertension is associated with decreased vascular responsiveness to vasoconstrictors, which may contribute to the hyperdynamics. Isosorbide dinitrate is an effective portal hypotensive drug. The present study aimed to investigate whether chronic administration of isosorbide dinitrate could affect vascular responsiveness in portal hypertensive rats. METHODS: Portal hypertension was induced by partial portal vein ligation. Sham-operated (Sham) rats served as controls. There were four animal groups for this study: portal vein ligation-isosorbide dinitrate group, portal vein ligation-vehicle (Veh) group, Sham-isosorbide dinitrate group and Sham-Veh group. Isosorbide dinitrate (5 mg x kg(-1) x 12 h(-1) was given by gavage for 8 days starting 1 day before ligation and continuing thereafter. Mesenteric arteries were removed for contractile study after hemodynamic measurement. RESULTS: Contractile responses to KCI (15-90 mM) and phenylephrine (10(-9)-10(-4) M) were recorded. Both vascular reactivity and sensitivity were significantly reduced in portal vein ligation rats as compared to Sham rats. Chronic isosorbide dinitrate treatment reduced portal venous pressure in portal vein ligation rats. Moreover, the maximal contractile responses to KCl and phenylephrine were significantly enhanced in both portal vein ligation and Sham rats after isosorbide dinitrate treatment, but relative hyporeactivity persisted in portal vein ligation rats. In contrast, a single dose of isosorbide dinitrate did not alter the contractile sensitivity or reactivity to KCl or phenylephrine in either portal vein ligation or Sham rats. CONCLUSION: Our results show that long-term administration of isosorbide dinitrate enhanced vascular contractility in both portal vein ligation and Sham rats, but relative hyporeactivity persisted in portal vein ligation rats.

Administration, Oral↗

PubMed1998

Structural modification of an orally active thrombin inhibitor, LB30057: replacement of the D-pocket-binding naphthyl moiety.

An amidrazonophenylalanine derivative LB30057 (2) was identified as a potent (Ki = 0.38 nM), selective, and orally active thrombin inhibitor. As a continuation of studies into benzamidrazone-based thrombin inhibitors, we have structurally modified compound 2 by replacing the naphthyl group with a variety of hydrophobic moieties. This study led to discovery of several compounds with significantly enhanced potency in thrombin inhibition without sacrificing selectivity against trypsin and oral absorption. The highest activity was obtained with compound 23 (Ki = 0.045 nM).

Administration, Oral↗