Pharmacokinetics of tramadol and o-desmethyltramadol in goats after intravenous and oral administration.

The aim of this trial was to implement a method to obtain a tool for analyses of tramadol and the main metabolite, o-desmethyltramadol (M1), in goat's plasma, and to evaluate the pharmacokinetics of these substances following intravenous (i.v.) and oral (p.o.) administration in female goats. The pharmacokinetics of tramadol and M1 were examined following i.v. or p.o. tramadol administration to six female goats (2 mg/kg). Average retention time was 5.13 min for tramadol and 2.42 min for M1. The calculated parameters for half-life, volume of distribution and total body clearance were 0.94+/-0.34 h, 2.48+/-0.58 L/kg and 2.18+/-0.23 L/kg/h following 2 mg/kg tramadol HCl administered intravenously. The systemic availability was 36.9+/-9.1% and half-life 2.67+/-0.54 h following tramadol 2 mg/kg p.o. M1 had a half-life of 2.89+/-0.43 h following i.v. administration of tramadol. Following p.o., M1 was not detectable.

Anxiolytic and anticonvulsant properties of doramectin in rats: behavioral and neurochemistric evaluations.

Doramecin is an antiparasitic drug that may interfere with gamma-aminobutyric acid (GABA) neurotransmission. Some behavioral manifestations are related with GABAergic neurotransmissions as anxiety and seizures. The objective of the present study was to examine the possible central nervous system (CNS) effects of doramectin (100, 300 and 1000 microg/kg, SC) in rats, using anxiety behavioral models, susceptibility to seizures and central neurotransmitter evaluations. The open-field results showed (i) few alterations in locomotion frequency; (ii) a biphasic effect on rearing frequency that may be the consequence of least habituation in open-field; (iii) the reduction of grooming durations might be attributed to a possible anxiolytic effect of doramectin since GABAergic agonists reduced this parameter in apparatus. Our data in the hole board showed no effects in locomotion and rearing frequencies but increased head dipping frequency of rats administered doramectin similarly to anxiolytic drugs. In plus-maze test, doramectin administration increased the number of entries and time into open arms, indicating also an anxiolytic effect. Doramectin protected animals from convulsant effects of picrotoxin, indicative of an anxiolytic pharmacological profile of a drug with GABAergic properties. The alterations observed in central dopaminergic, noradrenergic and serotoninergic neurotransmissions might be the consequence of reinforcement in central GABAergic neurotransmission induced by doramectin. The present results suggest that doramectin has the pharmacological profile of an anxiolytic/anticonvulsant drug with GABAergic properties.

Possible anxiogenic effects of fenvalerate, a type II pyrethroid pesticide, in rats.

Pyrethroids are insecticides extensively used to control pests around houses as well as in agriculture. It has been suggested that type II pyrethroids may act on GABA receptors as benzodiazepine antagonists. Because benzodiazepines are used in anxiety, the present study was undertaken to investigate the possible anxiogenic effects of fenvalerate, a type II pyrethroid, in rats. Behavior in the open-field, social interaction, plus-maze behavior, and one-way passive avoidance were studied in rats orally treated with 1, 10, or 30 mg/kg fenvalerate. This pyrethroid reduced locomotion and rearing frequencies and increased immobility duration. Ten and 30 mg/kg of fenvalerate reduced social interaction, whereas the 1 mg/kg dose had no effect on this behavior. Fenvalerate administration did not change the plus-maze behavior of rats. Pretraining administration (1, 10, and 30 mg/kg) did not modify the behavior of rats during the training session of a passive avoidance task, while in the test session 10 mg/kg fenvalerate caused an increase in the crossing latency, and the 30 mg/kg dose reduced this parameter and increased the percent of animals crossing to the shock compartment. The behavioral alterations observed in this study suggest that fenvalerate has an anxiolytic effect on rats.

Effects of monensin feeding during development on female rats and their offspring.

Monensin, a growth-promoting agent and coccidiostat used in veterinary medicine, was studied in terms of its effects on the development of female rats and their offspring when added to the diet. Young female rats received 100 or 300 ppm monensin mixed with powdered chow diet until adulthood, when they were mated and their offspring were evaluated for physical and neurobehavioural development. The data showed that 1) exposure to the higher monensin concentration reduced female body weight; no deaths occurred after exposure to the two monensin concentrations; 2) the offspring of the experimental group receiving 300 ppm monensin presented a weight reduction from 10 to 21 days of lactation; 3) incisor eruption was delayed only in females after exposure to the 100 ppm concentration. We conclude that exposure to monensin during development induces toxicity in female rats and has a notable adverse effect on growth with some limited effects on selective milestones of physical and functional development of the offspring during the postnatal period.

Croton zehntneri: possible central nervous system effects of the essential oil in rodents.

The effects of essential oil of Croton zehntneri (Euphorbiaceae), orally administered were studied on behavioral parameters using rats and mice. The oil suspension did not modify pentobarbital induced-hypnosis, stereotypic behavior, catalepsy and amphetamine-induced hypermotility. The open-field behaviors were decreased and the minimal convulsant dose of pentylenetetrazole was increased.

The diphenhydramine-induced decrease in general open-field activity of female rats is gonadal steroid dependent.

The effect of ovarian steroids on sedative effects of diphenhydramine (D), a histamine H1 receptor blocker, was determined. Seventy-five female Wistar rats were randomly divided into three groups: Group 1 (N = 54) was ovariectomized, group 2 (N = 7) was sham-operated, and group 3 (N = 14) was intact. The ovariectomized rats were then subdivided into 4 groups. Two groups received peanut oil 54 and 6 h before treatment with saline solution (group OS) or 20 mg/kg D (group OD). The other two groups received 50 micrograms/kg 17-beta-estradiol and 2 mg/kg progesterone, respectively, 54 and 6h before treatment with saline solution (group OHS) or 20 mg/kg D (group OHD). The sham-operated animals were treated as the OS group. Intact animals were injected with saline (group IS) or 20 mg/kg D (group ID) on the day of estrus, as determined by vaginal smears taken in the morning before the behavioral observations. Rats were observed for 6 min in the open field during the dark period of the cycle, 15 min after the administration of saline or D. There was a similar decrease in locomotion and rearing frequencies in OHS vs OHD and IS vs ID groups. Nevertheless, a lack of D sedative effect was observed in OD rats (locomotion and rearing frequencies, 56.0 +/- 3.3 vs 46.1 +/- 3.8 and 15.5 +/- 1.6 vs 15.2 +/- 1.6., for OS and OD groups, respectively). The results suggest that the sedative effect of diphenhydramine depends on the presence of ovarian steroids.

Effects of a Palicourea marcgravii leaf extract on some dopamine-related behaviors of rats.

The effects of a Palicourea marcgravii leaf extract on some dopamine-related behaviors were studied in rats. The extract given subcutaneously decreased both spontaneous locomotion and rearing frequencies of rats observed in open-field studies and increased their periods of immobility. The extract was also able to produce a rightward displacement of the apomorphine dose-response curve for stereotyped behavior and decrease the maximum response possible. Although the extract (1.87 g/kg subcutaneously) was unable to produce true catalepsy by itself, it potentiated that induced by haloperidol. These results with the extract can be interpreted to be due to a direct blocking action for the extract on a mesostriatal dopamine receptor or to an indirect effect on dopamine pathways through central cholinergic activation.

Effects of prenatal diphenhydramine administration on sexual behavior in rats.

In order to study the involvement of the brain histamine system on the sexual behavior of rats prenatally exposed to the histamine H1 receptor blockader, diphenhydramine (DPD), the female lordotic response and male sexual behavior were analyzed. The results show that the lordotic response in the prenatal DPD-treated rats was increased in relation to control animals. Impairment of male sexual behavior was indicated by an increase in ejaculation latency, in the number of mounts and a decrease in the number of ejaculations up to 30 min after the first intromission. Prenatal exposure to DPD thus appears to alter female and male sexual behavior on reaching adulthood.

Toxic effects of Mascagnia rigida in laboratory animals.

Mascagnia rigida (Malpigheacea) is a toxic plant to cattle in Brazil. The extract prepared from the dried leaves of M rigida was administered to rats, mice, guinea pigs, hamsters and rabbits. Rabbits were the best animal model to study the toxic effects of M rigida.

Chromatographic isolation of caffeine from Palicourea marcgravii.

Palicourea marcgravii (Rubiacea) is the major toxic plant to cattle in Brazil. We show the presence of the xanthinic alkaloid, caffeine, in this plant's leaves.