5-Methoxytryptamine, beta-methylcarboxylate hydrochloride (indorenate), a new antihypertensive agent, was examined for teratogenic-embryotoxic effects in the mouse at doses of 0 (control), 10, 20, 40, and 80 mg/kg/day. The compound was administered by gastric intubation on days 6-15 of gestation. On day 17, the dams were sacrificed, the number of live, dead, and resorbed fetuses recorded and mean pup weight determined. Teratological evaluation was carried out by visual inspection, alizarin red staining of the skeleton and Wilson's sections. Signs of overtoxicity in mothers were found in the high-dose groups. There were no differences between control and indorenate-treated groups in the number of implantations, live fetuses or anomalies. However, an embryotoxic effect was observed at 40 and 80 mg/kg, shown by increased resorptions and lower weight of pups at the higher dose.

5-Methoxytryptamine↗

PubMed1995

Relationship between pharmacokinetics and the analgesic effect of ketorolac in the rat.

The relationship between the pharmacokinetic properties and the analgesic effect of ketorolac was evaluated with the pain-induced functional impairment model in the rat. Female Wistar rats were injected with uric acid in the knee of the right hind limb to produce dysfunction. Then, animals received an oral dose of 0.3, 1, 1.8, 3.2 or 5.6 mg/kg of ketorolac tromethamine and analgesic effect and blood concentration, determined by high-performance liquid chromatography, were evaluated at selected times for a period of 4 hr. Ketorolac produced a dose-dependent analgesic effect, measured as a recovery of the functionality of the injured limb, which reached its maximal effect at doses of 3.2 mg/kg or higher. When functionality index was plotted against ketorolac blood concentration, a direct relationship was observed that was well described by the sigmoidal maximal effect model. The data strongly suggest that ketorolac's analgesic effect depends on the blood concentration of the drug.

Analgesics↗

PubMed1995

A comparative study of the effects of some 5-HT1A receptor agonists on the blood pressure of pithed rats.

The intention of this study was to supply additional information about direct effects of the 5-HT1A receptor agonist indorenate on the arterial blood pressure. The effects of indorenate were compared with those of buspirone and ipsapirone (all selective 5-HT1A agonists) on the blood pressure of pithed rats. These compounds increased the blood pressure in a dose-dependent fashion. The effects of either ipsapirone or buspirone were clearly inhibited with 100 micrograms/kg of prazosin (selective alpha 1-adrenoceptor antagonist), whereas 1 mg/kg of this blocker elicited only a mild inhibition of the pressor effect of indorenate. Pindolol (100 micrograms/kg; a beta-adrenoceptor and 5-HT1 receptor blocker) was unable to modify the effects of all the 5-HT1A agonists tested. In addition, the 5-HT2 receptor and weak alpha 1-adrenoceptor blocker ketanserin (10-100 micrograms/kg) antagonized the pressor effect of indorenate. Nevertheless, only a mild inhibition was observed in the case of both ipsapirone and buspirone. On the other hand, the latter drugs diminished the blood pressure of pithed rats intravenously infused with norepinephrine, but indorenate was inactive. However, in rats infused with quipazine, all the 5-HT1A agonists failed to reduce blood pressure. These results indicate that buspirone and ipsapirone behaved as partial alpha 1-adrenoceptor agonists. Furthermore, the results show that indorenate-elicited pressor effects are probably due to stimulation of 5-HT2 receptors. Thus, unlike ipsapirone and buspirone, indorenate did not show conclusively activity related with alpha 1-adrenoceptors.

5-Methoxytryptamine↗

PubMed1995

Evolution of Mexican pharmacology.

Explore the source record for details and available documents.

History, 19th Century↗

PubMed1995

Changes in endothelium-dependent vascular responses associated with spontaneous hypertension and age in rats.

The aim of this study was to investigate if the endothelium-dependent relaxation and the inhibitory effect of endothelium against vasoconstrictor stimuli are reduced by aging and hypertension in rat aorta. Both relaxation and isometric contraction of intact and denuded aortic rings from spontaneously hypertensive rats (SHR) of 7-9, 12-18, 28-36 and more than 70 weeks old and from age-matched Wistar-Kyoto rats (WKY) were measured in parallel. An age-related decrease of endothelium-dependent relaxation to acetylcholine was found, which was greater in arteries from SHR (p < 0.05). Indomethacin normalized the endothelium-dependent relaxations in aortic rings from either old or hypertensive rats. Relaxations elicited by nitroglycerin were slightly enhanced with age in both WKY and SHR (p < 0.05). Moreover, endothelium removal increased responsiveness to indanidine and to 5-hydroxytryptamine (5-HT). Endothelium-dependent inhibition on the contraction decreased with aging (to a greater extent in SHR). These results indicate that aging and hypertension are associated with a decrease in the endothelium-dependent responses. Endothelium-dependent relaxations of aortae from old normotensive and hypertensive rats were impaired by the production of a cyclooxygenase-derived contractile factor. However, the higher response to nitroglycerin suggests a lesser production of endogenous nitric oxide by endothelial cells.

Aging↗

PubMed1994

Lymphocyte proliferation kinetics and sister-chromatid exchanges in individuals treated with metronidazole.

Metronidazole, an effective agent for the treatment of protozoan infections, is frequently used in developing countries. However, the employment of this drug has been questioned in view of its mutagenicity in bacteria and carcinogenicity in mice. A genotoxic study was carried out in which cellular proliferation kinetics and the frequency of sister-chromatid exchanges were determined in human peripheral blood lymphocytes from 12 individuals treated with therapeutic doses of metronidazole. No effect was observed on mitotic index with the treatment, although a significant increase was found in three individuals after treatment. No increase of sister-chromatid exchanges was detected. The rate of lymphocyte proliferation kinetics showed an increase after the metronidazole treatment in all patients, indicating a possible immunostimulatory action.

Adult↗

PubMed1994

Comparative bioavailability of two oral formulations of ketorolac tromethamine: Dolac and Exodol.

The bioavailability of ketorolac after administration of two oral formulations containing 10 mg of ketorolac tromethamine, Exodol and Dolac, to 12 healthy Mexican volunteers was compared. Subjects received both formulations according to a randomized crossover design and blood samples were drawn at selected times during 24 h. Ketorolac plasma concentrations were determined by HPLC and individual plasma-concentration-against-time curves were constructed. Maximal plasma concentration and AUC0-24 values were compared by analysis of variance followed by Westlake's confidence interval test. 90% confidence limits ranged from 80 to 125% for Cmax and from 85 to 118% for AUC0-24. It is concluded that the two assayed formulations are bioequivalent.

Administration, Oral↗

PubMed1994

Mechanism of action of 8-OH-DPAT on learning and memory.

It has been previously demonstrated that pretraining injection of 8-hydroxy-2-(di-n-propilamino)tetralin (8-OH-DPAT, a 5-HT1A agonist) impairs conditioned response (CR) in an autoshaping learning task. Therefore, in the present work we intended to determine whether such an effect could be prevented by pretraining, and whether pre- or postsynaptic 5-HT receptors are involved. Groups of rats received or did not receive food magazine training. On the next day, all groups in both conditions, pre- or posttraining, were treated with 8-OH-DPAT (0, 0.062, or 0.250 mg/kg). Posttraining groups were tested on a second session of autoshaping 24 h later. In a second experiment, naive rats received para-chlorophenylalanine (PCPA) (300 mg/kg x 3 days) before pre- or posttraining injection of 8-OH-DPAT. Results showed that in those groups trained to food magazine and treated 24 h later with 8-OH-DPAT, CR was not affected or enhanced. PCPA injection had no effect by itself, but blocked or attenuated the effect of a post- or pretraining injection of 8-OH-DPAT. The present data suggest that a) the pretraining effect of 8-OH-DPAT eliciting a decrease in CR can be eliminated by a food magazine training session; and b) presynaptic 5-HT1A receptors are involved in the effect of 8-OH-DPAT on the acquisition and consolidation of learning.

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

PubMed1994

Hydrophilic-hydrophobic biodegradable polymers: release characteristics of hydrogen-bonded, ring-containing polymer matrices.

Biodegradable hydrogen-bonded, ring-containing polymers were prepared. These included poly(enolketones) by the controlled oxidation of poly(vinyl alcohol), and poly(amide-amines) and poly(amide-enamine-esters) by the reaction of diketene with diamines. These polymers had both hydrophilic and hydrophobic properties and are potentially matrix materials for the controlled release of drugs.

Biodegradation, Environmental↗

PubMed1994

Modification of 8-OH-DPAT effects on learning by manipulation of the assay conditions.

A role for the 5-HT1A receptor in learning and memory has been suggested by diverse evidence. The present paper deals with the acute effect of 8-OH-DPAT (a 5-HT1A agonist) administered to rats before or after training in an autoshaped lever-press response (a model of associative learning). The results show that 8-OH-DPAT improved consolidation of the conditioned response (CR) when injected post-training, but impaired it with pretraining administration. Both effects were time-dependent. When the compound was administered pre- or post-training to free-feeding or prefeeding animals, they did not learn the CR. When it was administered to retrained food-deprived animals, the compound was also inactive. However, with retrained animals on a free-feeding schedule, pre- or post-training administration of 8-OH-DPAT enhanced retrieval in a dose-dependent fashion. Pretraining administration of 8-OH-DPAT impaired food intake and exploration, and therefore learning. The present results strongly suggest a role of 5-HT1A receptors in the consolidation and retrieval of learning. Such improvement is independent of food intake.

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

PubMed1994

Effect of ozone exposure on antigen-induced airway hyperresponsiveness in guinea pigs.

Airway hyperresponsiveness can be induced by several stimuli including antigen and ozone, both of which may be present in the air of polluted cities. Though the effect of ozone on the bronchoconstrictor response to antigen has been well described, the combined effect of these stimuli on airway hyperresponsiveness has not yet been studied. Sensitized guinea pigs with or without ozone exposure for 1 h at 3 ppm, 18 h prior to study, were challenged with a dose-response curve to histamine (0.01-1.8 micrograms/kg, iv) followed by an antigen challenge (ovalbumin, 50 micrograms/kg, iv), and then by a second histamine dose-response curve 1 h later. Airway responses were measured as the increase in pulmonary insufflation pressure. In sensitized guinea pigs, the histamine ED50 significantly decreased after antigen challenge, demonstrating the development of airway hyperresponsiveness. Sensitized guinea pigs exposed to ozone showed airway hyperresponsiveness to histamine when compared with nonexposed animals, and such hyperresponsiveness was further enhanced after antigen challenge. We conclude that in this guinea pig model of acute allergic bronchoconstriction both antigen challenge and ozone induce airway hyperresponsiveness, while ozone exposure does not modify the development of antigen-induced hyperresponsiveness.

Acute Disease↗

PubMed1994

Inhibition of serotonin-induced increase in canine external carotid blood flow by drugs that decrease the sympathetic outflow.

1. The present study was designed to analyse the effect of the centrally-acting sympatho-inhibitory drugs, prazosin and ketanserin, on the increase in external carotid blood flow (external CBF) produced by 5-hydroxytryptamine (5-HT) in pentobarbital-anaesthetized dogs. 2. Intracarotid (i.c.) infusions of 5-HT (10 micrograms min-1 during 1 min) produced an increase in external CBF without changes in mean arterial blood pressure or heart rate. This response to 5-HT was dose-dependently blocked by intravenous (i.v.) administration of prazosin (1, 3, 10, 30 and 100 micrograms kg-1) or ketanserin (10, 30, 100 and 300 micrograms kg-1). 3. Furthermore, 5-HT-induced increase in external CBF was inhibited by either the ganglionic blocking agent, mecamylamine (0.03, 0.1, 0.3, 1, 3 and 10 mg kg-1), the mixed 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (3, 10 and 30 micrograms kg-1) or the 5-HT1A ligand, spiroxatrine (10, 30, 100 and 300 micrograms kg-1). In contrast, the selective 5-HT2 and 5-HT1C receptor antagonist, ritanserin (30 and 100 micrograms kg-1, i.v.), was unable to block the above response to 5-HT. 4. It is concluded that the inhibition of 5-HT-induced increase in external CBF by prazosin, ketanserin, mecamylamine and spiroxatrine is due to a reduction in the sympathetic tone and not to a blockade of 5-HT receptors.

Animals↗

PubMed1994

Determination of ketorolac in blood and plasma samples by high-performance liquid chromatography.

A new method for determination of ketorolac in blood or plasma samples by reversed-phase high-performance liquid chromatography has been developed. The method includes a double extraction with diethyl ether and detection by absorbance at 313 nm. Quantitation was performed by height ratios of ketorolac and the internal standard (sodium tolmetin). Detection limit of the method was 3 ng/ml using 1 ml of plasma and 10 ng/ml using 0.2 ml of blood. The method is linear in the range of concentrations typically obtained after therapeutic doses of the drug, has the advantages of using low volume of body fluid and the internal standard used is commercially available. Those characteristics allow us to conclude that this method is suitable for pharmacokinetic or drug monitoring studies.

Animals↗