The imidazol and imidazoline derives have many advantages in therapy. For the synthesis of new imidazoline derives, the authors implemented the ethylene diamene cyclization from nitril compounds differently substituted. Then, a dehydrogenation of these imidazolines leaded to the imidazol derives. The last reaction consisted of the condensation of these imidazolines and imidazoles. The authors subjected their synthesized products to an ophthalmic protective evaluation (anti-oedema, secondary anti-hyperemia) on the experimental ocular irritancy models
Imidazolines ; Cyclization

Acetohydroxyacid synthase (AHAS) catalyses the first reaction in the pathway for synthesis of the branched-chain amino acids. AHAS is the target for sulfonylurea, imidazolinone and other AHAS-inhibitor herbicides. Herbicides-resistant AHAS genes have potential application in plant transgenetic engineering and development of new generation herbicide. The AHAS isozyme genes ilvBN, ilvGM and ilvIH were cloned from metsulfuron-methyl resistant strain Klebsiella sp. HR11 and metsulfuron-methyl sensitive strain Klebsiella pneumoniae MGH 78578. Homologous sequences comparison indicated that the differences in AHAS isozyme genes at amino acid levels between strain HR11 and strain MGH 78578 were mainly on the large subunits of ilvBN and ilvGM. The three AHAS isozyme genes from HR11 and MGH 78578 were ligated into the expression vector pET29a(+) and expressed in Escherichia coli BL21, respectively. The results of enzyme inhibition assay showed that only ilvBN and ilvGM from strain HR11 showed strong resistance to AHAS-inhibitor herbicides, while ilvIH from strain HR11 and ilvBN, ilvGM and ilvIH from strain MGH78578 were sensitive to AHAS-inhibitor herbicides.
Acetolactate Synthase ; chemistry ; genetics ; Escherichia coli ; genetics ; metabolism ; Gene Expression ; Genes, Bacterial ; drug effects ; Herbicide Resistance ; genetics ; Herbicides ; pharmacology ; Imidazolines ; pharmacology ; Isoenzymes ; genetics ; Klebsiella ; genetics ; Sulfonylurea Compounds ; pharmacology

AIMTo design and synthesize new arylsubstituted imidazolin-2-one analogues as antitumor compounds.

METHODSArylsubstituted imidazolin-2-ones were prepared by condensation the appropriate omega-amino-acetophenone hydrochloride with arylisocyanate in toluene. The target compounds prepared in this study were tested for cytotoxicity against PC-3, A549, HO-8910, Hela, HL60, K562 and HL60R cancer cell lines, and mechanism of one of the products 4y was further evaluated with its mechanium.

RESULTSThirty-six new compounds were synthesized and confirmed by 1H NMR, MS and elemental analysis. One of the synthesized products, compound 4y, displayed an encouraging selective activity against HL60 cells, and it was partlydue to the cell cycle arrest and cell apoptosis.

CONCLUSIONCompound 4y is worthy to be intensively studied.

Amides ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; HL-60 Cells ; Humans ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Imidazolines ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure

The central dopaminergic receptor is believed to suppress the cardiovascular system So it may be involved in the blood pressure regulation But, it's action is still controversial. Furthermore, the mechanisms involved in the central dopaminergic receptor-induced blood pressure regulation is unclear. So, present study was performed in order to clarify the effects of central dopaminergic receptor and to investigate the mechamisms involved in it. Lisuride a D2-receptor agonist, and clonidine, a alpha2-receptor agonist, were administered into lateral ventricle in rat and the changes of blood pressure were compared The results were as follows; 1. Intracerebroventricular administration of lisuride amd clonidine from 0.3 ug to 10 ug elicited dose related decrease of blood pressure and heart rate. The potencies were similar in both drugs. 2. Centrally administered sulpiride, a D2-antagonist, blocked only the lisuride-induced hypotension while the clonidine induced hypotension was blocked only by centrally adrninistered tolazoline, a alpha2-antagonist. Intravenous administration of both antagonists elicited no or minimal attenuabon of agonists effects. 3. After desipramine pretreatment, which increases the norepinephrine concentration lisuride elicited somewhat further decrease of blood pressure than normal, while clonidine administration caused rather increase in blood pressure. 4. After chemical sympathectomy by 6-hydroxydopamine, lisuride administration still elicited strong suppression of blood pressure. From thses above results, it is concluded that central dopaminergic receptor activation decrease the blood pressure. Suppression of the norepinephrine release at the sympathetic nerve terminal is not related with central dopaminergic receptor induced hypotension.
Administration, Intravenous ; Animals ; Blood Pressure ; Cardiovascular System* ; Clonidine ; Desipramine ; Heart Rate ; Hypotension ; Lateral Ventricles ; Lisuride ; Norepinephrine ; Oxidopamine ; Rats ; Sulpiride ; Sympathectomy, Chemical ; Tolazoline

No abstract available.
Bupivacaine* ; Clonidine* ; Yohimbine

Background: Epidural anesthesia is a widely used anesthesia technique commonly for surgeries involving the lower extremities up to the abdomen.It is beneficial for long duration surgeries because the epidural catheter in place allows additional of local anesthetic as needed. However, this technique has a slower onset of action and requires a larger volume of local anesthetic compared with spinal anesthesia. This study aims to determine if clonidine when used as an adjuvant can hasten the onset of action of levobupivacaine epidural anesthesia thus allowing the early commencement of surgery. Methodology: This is a double blind randomized controlled trial. After approval from the institution‘s research ethics and review committee,a total of 36 patients of American Society of Anesthesiologist ClassificationI or II for elective lower limb orthopedic surgery under levobupivacaine epidural anesthesia were purposively enrolled in this study and randomly assigned by match pairing of characteristics to two groups: GroupA—Clonidine and Group B—plain normal saline solution. Group A were given 0.5% levobupivocaine 15cc with 30 yg (0.2cc) clonidine and groupB were given 0.5% levobupivocaine 15cc with 0.2cc plain normal saline solution. In both groups the onset of levobupivacaine epidural anesthesia (sensory block atT10dermotomal level/Bromage 1) were observed. Side effects such as hypotension, decreased in respiratory rate, oxygen saturation, and any untoward incidence were noted. All data gathered: statistical mean, median, standard deviation, and T test were analyzed using the SPSS software at 5% significance level. Results: The mean onset of action of group A— Clonidine group (5.62 minutes) was foster compared to group B—control (11.33 minutes), which was statistically significant (P«0.05). The highest dermotomal level for the clonidine group was at T6 and T7forthecontrol group. Two segments regression was at 180 minutes forthe Clonidine group while 60 minutes for the control group. The patients given clonidine experienced side effects such as sedation, bradycardio (20% decrease in cardiac rote from baseline), and shivering. Hypotension was not observed in both clonidine and control groups. Conclusion Clonidine ata dose of30 |Jgwhen used as an adjuvant to levobupivacaine epidural anesthesia can hasten its onset of action among patients undergoing elective lower limb orthopedic surgery.
Anesthesia, Epidural ; Clonidine

The antihypertensive effect of clonidine was evaluated in 129 patients with essential hypertension of mild to moderate severity with a dosage of one tablet(0.075mg) a day for 71 patients of Group I and two tablets a day for 58 patients of Group II. The results were as follows : 1) Of 71 patients of Group I, 34 patients(47.9%)showed good antihypertensive effect(greater than 15 mmHg drop in mean diastolic pressure) and 11 patients(15.5%) showed fair effect(10-14 mmHg drop in mean diastolic pressure). 2) Of 58 patients of Group II, 39 patients(67.2%) showed good effect and 7 patients(12.1%) showed fair effect. 3) The side effect observed was transient and tolerable dry mouth, which developed in 5.6% of Group I patients and 13.6% of Group II patients.
Clonidine* ; Humans ; Hypertension ; Mouth ; Tablets

No abstract available.
Clonidine ; Horner Syndrome ; Meningitis, Viral

1) The author investigated whether presynaptic alpha-adrenoceptors exist in the cardioaccelerator nerves of cold-blooded animals(frog, tortoise) as in ones of in mammals. 2) Each atrial preparation of a frog, tortoise and guinea-pig produced the positive chronotropic and inotropic responces to field stimulation. Each ventricular muscle preparation of frog and tortoise produced positive inotropic responces to field stimulation. 3) Both the responces of frog atrium and the inotropic response of frog ventrice to the stimulation were abolished or markedly inhibited by the presence of tetrodotoxin, guanethidine and proparanolo. Both responses of tortoise atrium to the stimulation were markedly inhibited by propranolol and the inotropic response ventricle to the stimulation was markedly inhibited by tetrodotoxin. 4) Both responses of frog and tortoise atrium, and the inotropic response of frog and tortoise ventricle to the stimulation were not affected by clonidine and yohimbine. 5) Both responses of guinea-pig atrium to the stimulation were markedly inhibited in the presence of clonidine and this clonidine-induced inhibition was not observed in the presence of yohimbine. 6) The above results suggest that presynaptic alpha-adrenoceptors do not exist in the cardioaccelerator nerves of frog and tortoise, being different from those of mammalisn animals.
Animals* ; Clonidine ; Guanethidine ; Mammals ; Propranolol ; Tetrodotoxin ; Yohimbine

BACKGROUND: Clonidine is an alpha2-adrenergic drug used for analgesic effect, reducing sympathetic stimulation and anesthetic requirement. We examined the analgesic effect of clonidine on incisional pain after its intrathecal administration using a rat postincisional model. METHODS: After an intrathecal (IT) catheter insertion in 20 Spraw Dawley rats, they were divided into two groups; one group (Group S, n = 10) received a saline 20microl injection through an IT catheter, and another (Group C, n = 10) received clonidine 20microgram in 10microl volume followed by another 10microl of saline for washing the catheter. The measurements of the threshold of tactile allodynia (TTA) were performed at 20, 40, 60, 80, 120, 180 and 240 mins after the IT injection. Additionally, 1, 2 and 3 days after the first IT injection, IT injection and the measurements of TTA of pre- and post-injection were repeated. The measurements of TTA were performed in both areas, 5 mm (N-area) and 10 mm (R-area) away from incision by using von Frey hair and up-down method. RESULTS: TTA (N-area) and TTA (R-area) during 4 hours after IT injection in Group C were greater than those in Group S (P< 0.05). TTA (N-area) of post-injection 2 and 3 days after the first IT injection were greater than those of pre-injection in Group C (P< 0.05), and TTA (R-area) after the IT injection 1, 2 and 3 days after the first IT injection were greater than those of pre-injection in Group C (P< 0.05). CONCLUSIONS: A single IT injection of clonidine 20microgram had analgesic effects lasting more than 4 hours in the rat postincisional model. Additional IT clonidine could show antiallodynic effects during three days after the first IT clonidine.
Animals ; Catheters ; Clonidine* ; Hair ; Hyperalgesia ; Rats*