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Biomedical subjects

E Hong

Publications and source records attributed to E Hong.

At least 91 records · Page 5Linked to original sources
PubMed1994

Determination of oral rifampin pharmacokinetic parameters in Mexicans and comparison with other populations: absence of evidence for interethnic variability.

Oral pharmacokinetics of rifampin were studied in eight Mexican young healthy male volunteers after administration of a 600 mg oral dose. After an overnight fast, subjects received medication and blood samples were drawn at selected times over a 24-h period. Rifampin plasma levels were determined by HPLC. Pharmacokinetic parameters (mean +/- SEM) were: Cmax 13.514 +/- 1.775 micrograms/ml, tmax 1.88 +/- 0.30 h, AUC 73.61 +/- 9.48 micrograms.h/ml and half-life 2.98 +/- 0.29 h. Results were compared with those obtained for other populations under similar conditions in order to explore the possibility of interethnic variability, since it has been reported that rifampin pharmacokinetics in Indonesian subjects differ from those found in Europeans. Pharmacokinetic data found in Mexicans were comparable with those observed in British, Indian, Japanese and Italian individuals. As the pharmacokinetics of rifampin seem to be similar in different populations, it is concluded that ethnic origin does not appear to play an important role. Therefore, dosing regimens designed for Caucasians can be extrapolated for other populations.

Administration, Oral↗
PubMed1994

Pharmacological screening of some quinoline derivatives in canine vascular smooth muscle.

In order to develop drugs which can discriminate vascular 5-HT1-like receptors, this study analyzed the agonist/antagonist interactions of several quinoline derivatives in vascular tissues containing these receptors. 5-HT and several substituted quinolines were evaluated and compared in canine basilar artery rings and saphenous vein helical strips which were mounted in organ baths for monitoring isometric tension changes. Based upon the molecular features of quipazine, the main assayed variations included some substitutions at the 4-position of piperazine and miscellaneous substitutions at the 2-position of the quinoline nucleus. The results, in terms of agonist-induced contraction and/or antagonism of 5-HT-induced contraction revealed that: a) 4-alkylation of the piperazinyl moiety moderately increases the agonist efficacy; b) halogenation or methylation at 5- or 6-position of both 1-piperazinyl- and 4-methyl-1-piperazinyl quinolines completely abolishes agonist activity; c) introduction of larger substituents (i.e., alkyl, carbethoxy, acethoxyalkyl, aromatic and non-aromatic rings) at the 4-position of the piperazinyl moiety, notably decreases or even abolishes the agonist activity; d) replacement of the piperazinyl group by an amino-ethyl moiety importantly increases potency (more than threefold) and efficacy (more than twofold). These findings represent leads which may aid the subsequent design of vascular 5-HT1-like-selective agents.

Animals↗
PubMed1993

Pharmacological evidence for interactions between 5-HT1A receptor agonists and subtypes of alpha 1-adrenoceptors on rabbit aorta.

This study was designed to determine if alpha 1-adrenoceptors are involved in the vascular responses to 5-HT1A receptor agonists. Buspirone (3.1 x 10(-7)-3.1 x 10(-5) M) and 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT; 3.1 x 10(-6)-10(-4) M) elicited contractions of rabbit aorta rings which were blocked by prazosin (10(-9)-5.6 x 10(-9) M), but which were unaffected by reserpine pretreatment (1 mg/kg i.p.). 5-Methylurapidil (10(-7) and 10(-6) M) blocked contractions elicited by 8-OH-DPAT and by buspirone, whereas chloroethylchonidine (10(-5) and 10(-4) M) inhibited only the effect of buspirone. In addition, these 5-HT1A receptor agonists relaxed arteries precontracted with alpha-adrenoceptor agonists in a similar range of concentrations in which they elicited contraction. Moreover, 8-OH-DPAT and buspirone protected the alpha-adrenoceptors from the irreversible blockade provoked by phenoxybenzamine (10(-7) M), as judged by the norepinephrine contraction and stimulated phosphatidylinositol labeling. According to these results the contractile and relaxant effects elicited by 5-HT1A receptor agonists are a consequence of a direct interaction with alpha 1-adrenoceptors. The contraction elicited by 8-OH-DPAT may be mediated by alpha 1A-adrenoceptors, whereas both alpha 1A- and alpha 1B-adrenoceptors may mediate the effect of buspirone in rabbit aorta.

Adrenergic alpha-Agonists↗
PubMed1993

Role of 5-HT1-like receptors in the increase in external carotid blood flow induced by 5-hydroxytryptamine in the dog.

This study investigated the receptor involved in the 5-hydroxytryptamine (5-HT)-induced increase in external carotid blood flow in pentobarbital-anaesthetized dogs. One-minute intracarotid (i.c.) infusions of 5-HT (0.3, 1, 3 and 10 micrograms) and 5-carboxamidotryptamine (5-CT; 0.01, 0.03, 0.1 and 0.3 micrograms) produced dose-dependent increases in external carotid blood flow without changes in mean arterial blood pressure or heart rate. After vagosympathectomy, the above vasodilator responses to 5-HT and 5-CT were abolished and remained so even after restoration of carotid vascular tone with noradrenaline. Furthermore, the 5-HT- and 5-CT-induced increases in external carotid blood flow were not modified by the 5-HT2 receptor antagonist, ritanserin (100 micrograms/kg i.v.), nor the 5-HT3 receptor antagonist, 1 alpha H,3 alpha, 5 alpha H-tropan-3yl-3,5-dichlorobenzoate (MDL 72222; 140 micrograms/kg i.v.), but were potently and dose dependently antagonized by the mixed 5-HT1-like and 5-HT2 receptor blocker, methiothepin (3, 10 and 30 micrograms/kg i.v.). Interestingly, the 5-HT1A and 5-HT1B receptor antagonist, cyanopindolol (100, 300 and 1000 micrograms/kg i.v.), blocked the effects of 5-HT, but the block was not elicited in a dose-dependent manner, with only the response induced by 0.3 microgram/min 5-CT being significantly antagonized by the highest dose of cyanopindolol; however, this blockade was not selective. Unlike 5-HT and 5-CT, 1 min i.c. infusions of either the 5-HT1C/5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI; 30-300 micrograms), or the 5-HT3 receptor agonist, 2-methyl-5-HT (10-300 micrograms), were devoid of effects on the canine external carotid blood flow. It is concluded that the 5-HT-induced increase in external carotid blood flow is mediated by 5-HT1-like receptors probably located on carotid sympathetic nerves. These receptors, however, do not seem to correspond to either the 5-HT1A, 5-HT1B or 5-HT1C receptor subtypes.

Acetylcholine↗
PubMed1993

Modification of the anxiolytic effects of 5-HT1A agonists by shock intensity.

Contradictory evidence exists concerning the anxiolytic effects of 5-HT1A agonists in the conflict test. In the present work, a modification of the Vogel conflict model was used to assess different doses of diazepam (0.1-5.6 mg/kg), ipsapirone (1.0-17.8 mg/kg), buspirone (1.7-17.8 mg/kg), and indorenate (0.56-17.8 mg/kg) in rats receiving two different electric shock intensities (0.16 and 0.32 mA). The results show that the three 5-HT1A agonists had a smaller anticonflict effect than diazepam. The anticonflict effect with each compound was of a greater magnitude at 0.16 mA intensity than at 0.32 mA. This study shows that, using different electric shock intensities, compounds produce a differential effect: the anticonflict effects were more pronounced with the lower electric shock intensity than with the higher intensity. The present results suggest that the use of different shock intensities can play distinct roles over the drug's effect in the conflict test.

5-Methoxytryptamine↗
PubMed1993

Learning styles of gifted adolescents with in-school versus out-of-school accomplishments in literature.

The learning styles of two groups of adolescents gifted in literature, one composed of subjects with high grade point averages in school in literature (n = 232) and one of subjects who had high scores on talented out-of-school accomplishments in literature (n = 192), were compared. Six of the 22 elements measured by the Learning Styles Inventory distinguished between the two groups. The out-of-school gifted group preferred to work with peers and felt comfortable learning in a variety of different ways. They tended to be less visual and more auditory learners and expressed a greater preference to learn by experiential or hands-on activities than the in-school gifted group. The implications for teaching and counseling gifted learners, differently defined, are discussed.

Adolescent↗
PubMed1993

Influence of sympathetic tone on the reactivity to indorenate in the external carotid vascular bed of the dog.

The present study was designed to analyze the effects of drugs that interfere with sympathetic transmission on the external carotid vasodilator response induced by the 5-HT1A receptor agonist, indorenate, in pentobarbital-anesthetized dogs. Intracarotid (i.c.) infusions of indorenate (1000 micrograms/l min) produced an increase in external carotid blood flow (external C.B.F.) without modifying mean arterial blood pressure or heart rate. This effect of indorenate was dose-dependently antagonized by intravenous (i.v.) administration of the alpha 1-adrenoceptor antagonist, prazosin (1, 3.1, 10, 31 and 100 micrograms/kg), the ganglionic blocking agent, mecamylamine (0.031, 0.1, 0.31, 1, 3.1 and 10 mg/kg) or the 5-HT2 receptor and alpha 1-adrenoceptor antagonist, ketanserin (10, 31 and 100 micrograms/kg). It is concluded that indorenate-induced increase in canine external C.B.F. is dependent on the vascular neurogenic tone.

5-Methoxytryptamine↗
PubMed1993

Vascular effects of ipsapirone are related with subtypes of alpha 1-adrenergic receptors.

The aim of this study was to provide further evidence about the participation of alpha 1-adrenoceptors in the vascular responses elicited by ipsapirone. This 5-HT1A agonist displayed vasodilator activity only when aortic rings were precontracted by alpha-adrenergic compounds. The relaxant effect was particularly evident when rings were precontracted with methoxamine (selective alpha 1A-adrenergic agonist). On the other hand, ipsapirone but not chloroethylclonidine (selective alpha 1B-adrenergic antagonist), clearly displaced norepinephrine and methoxamine vasocontractile concentration-response curves to the right. Finally, ipsapirone protected the alpha-adrenoceptors form the irreversible blockade provoked by phenoxybenzamine, as judged by the norepinephrine contraction and stimulated phosphatidylinositil labeling. Accordingly the relaxant effect elicited by ipsapirone in aortic rings precontracted with alpha-adrenergic agonists and the protective action against blockade by phenoxybenzamine shown by this agent are proof of its ability to occupy alpha 1-adrenoceptors. Specifically, alpha 1A-adrenergic receptors seem to be involved in ipsapirone vascular effects, since this agent selectively relaxed aortic preparation precontracted with methoxamine and unlike chloroethylclonidine, clearly inhibited the contractile effect of this agonist. In summary, the present findings can be explained by accepting that ipsapirone may act as an antagonist at alpha 1A-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1992

Species differences in the mechanism through which the serotonergic agonists indorenate and ipsapirone produce their anxiolytic action.

The effect of three anxiolytic drugs, indorenate, ipsapirone and diazepam, on the burying behaviour of rats and mice was studied. All three drugs induced a reduction in burying behaviour interpreted as a reduction in anxiety. However, a species difference in the diazepam sensitivity was found: rats showed a clear effect after 1.0 mg/kg while already at 0.25 mg/kg an action was observed in mice. The serotonergic anxiolytics produced similar responses at similar doses (2.5-5.0 mg/kg) in both species. The serotonergic antagonists, pindolol (3.1 mg/kg), alprenolol (5.0 mg/kg) and methiotepin (0.31 mg/kg), induced a slight reduction in the time spent burying but effectively counteracted the anxiolytic action of the serotonergic agonists in mice but not in rats. By contrast, in rats, the beta blocker, practolol (0.5 mg/kg), was the only drug effective in preventing the anxiolytic actions of ipsapirone. The combined treatment of indorenate and methiotepin resulted in an impairment of motor coordination and ambulatory behaviour in both species studied, thereby suggesting that the lack of effect of such combination was mediated by altering the motor behaviour. Finally, the reduction in ambulatory behaviour in mice produced by ipsapirone was effectively prevented by the antagonists methiotepin, pindolol and alprenolol indicating the involvement of a serotonergic receptor in this effect. From these results it is concluded that a different mechanism underlies the anxiolytic actions of indorenate and ipsapirone in mice and rats.

5-Methoxytryptamine↗
PubMed1992

Alpha 1-adrenoceptor blocking properties of spiroxatrine in rat aorta.

This preliminary study has analyzed the potential ability of the 5-HT1A ligand spiroxatrine to interact with vascular alpha 1-adrenoceptors. Norepinephrine and the selective alpha 1-adrenoceptor agonist, methoxamine, elicited concentration-dependent contractions of rat aortic rings. In contrast, (+/-)-spiroxatrine (from 10(-8) to 3.1X10(-7) M) was devoid of any effect on vascular tone per se, but shifted the concentration-response curves of norepinephrine and methoxamine to the right in a concentration-dependent manner with pA2 values of 8.48 +/- 0.22 and 8.93 +/- 0.33, respectively. Endothelium removal did not significantly affect the above pA2 values of (+/-)-spiroxatrine. These data, taken in concert, support the contention that (+/-)-spiroxatrine displays alpha 1-adrenoceptor blocking properties in rat aortic rings.

Adrenergic alpha-Antagonists↗
PubMed1992

Pharmacokinetics and antihypertensive effect of oral pelanserin in renal hypertensive dogs.

The pharmacokinetics and antihypertensive effect of pelanserin (CAS 2208-51-7), a 5-HT2- and alpha 1-antagonist, were studied during repetitive administration (0.5 mg/kg, p.o., b.i.d.) in renal hypertensive dogs. After the first dose, pelanserin was absorbed reaching a Cmax value of 39.6 +/- 9.01 ng/ml at a tmax of 2.58 +/- 0.74 h. The steady state of plasma levels was reached between the 3rd and 15th doses of pelanserin. Pharmacokinetic parameters calculated after the 47th dose of pelanserin were Cmax(ss) of 147.15 +/- 35.88 ng/ml at a tmax(ss) of 3.17 +/- 1.02 h, AUC(0-12 h) of 593.80 +/- 106.96 ng.h/ml and a terminal half-life of 18.02 +/- 2.94 h. The accumulation ratio determined as Cmin(ss)/Cmin1 was 2.36 +/- 0.43 and was similar to that calculated in basis to the terminal half-life 2.67 +/- 0.37. On the other hand, pelanserin produced blood pressure decrease with two different profiles. After the first dose an acute antihypertensive effect was observed which reached a maximum of 20 mmHg in about 3 h; then blood pressure recovered gradually arriving to basal values at 12 h. When administered repetitively, pelanserin produced a gradual reduction in blood pressure which reached its maximum at 15 days. After the last dose, blood pressure basal values were about 20 mmHg lower than pretreatment levels and remained almost unchanged during 48 h after the last dose. It is concluded that pelanserin pharmacokinetic and pharmacodynamic profiles in dogs are adequate for an antihypertensive agent, therefore this drug possesses potential therapeutic usefulness in the treatment of hypertension.

Animals↗