Simultaneous recording of uterine and tubal motility during utero-tubal insufflation in monkeys.

One main cause of female infertility is the tubal factor, and interest in the role and function of the Fallopian tube has increased our knowledge about tubal infertility. In this study in monkeys, Cynomolgus (Macaca fascicularis), the tubal and uterine motility was recorded with a Millar microtransducer. The recordings were made during uterotubal, uterine as well as tubal insufflation with gas. Tubal activity patterns varied with the phase of the menstrual cycle. The kymograms made during gas insufflation did not reflect tubal or uterine activity, as registered by the Millar microtransducer, but rather the resistance to pressure of the intra-uterine part of the tube. An intra-uterine pressure up to 200 mmHg, has previously been regarded as being free from risk of uncontrolled escape of gas outside the uterus and the oviducts. This was not confirmed in the present study.

Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography.

Two substituted benzamides, FLB 524 and raclopride, were labeled with 11C and examined for their possible use as ligands for positron emission tomography (PET)-scan studies on dopamine-2 (D-2) receptors in the brains of monkeys and healthy human subjects. Both ligands allowed the in vivo visualization of D-2 receptor binding in the corpus striatum caudate nucleus/putamen complex in PET-scan images. [11C]Raclopride showed a high ratio of specific striatal to nonspecific cerebellar binding, and the kinetics of binding of this ligand made it optimal for PET studies. The in vivo binding of [11C]raclopride in the striatum of cynomolgus monkeys was markedly reduced by displacement with haloperidol. This and previous in vitro data indicate that [11C]raclopride binds selectively to striatal D-2 dopamine receptors. In healthy human subjects, [11C]raclopride binding in the caudate nucleus/putamen was 4- to 5-fold greater than nonspecific binding in the cerebellum. In comparison with previously available ligands for PET-scan studies on central dopamine receptors in man, [11C]raclopride appears to be advantageous with regard to (i) specificity of binding to D-2 receptors, (ii) the high ratio between binding in dopamine-rich (caudate, putamen) and dopamine-poor (cerebellum) human brain regions, and (iii) rapid association and reversibility of specific binding. [11C]Raclopride should be a valuable tool for characterizing D-2 receptors in the brains of patients with neuropsychiatric disorders.

Imaging of [11C]-labelled Ro 15-1788 binding to benzodiazepine receptors in the human brain by positron emission tomography.

The benzodiazepine antagonist Ro 15-1788 was labelled with [11C] and examined for possible use as ligand for PET scan studies on benzodiazepine receptors in the brain of cynomolgus monkeys and human subjects. [11C] Ro 15-1788 allowed the in vivo visualization of benzodiazepine receptor binding in cerebral and cerebellar cortical areas as well as in basal brain nuclei in PET scan images. [11C] Ro 15-1788 exhibited a high ratio of specific benzodiazepine receptor binding (cerebral cortex) to non-specific binding (pons) and the kinetics of binding should be satisfactory for quantitative clinical PET scan studies using [11C]. The in vivo binding of [11C] Ro 15-1788 in the cerebral cortex of cynomolgus monkeys and healthy human subjects was reduced by approximately 90% within 10 min after the intravenous injection of a high dose of unlabelled Ro 15-1788 (0.5 mg/kg i.v.). Different areas of the healthy human brain showed an approximately 10-fold variation in maximal [11C] Ro 15-1788 binding that corresponded to the previously known distribution of benzodiazepine receptors in these regions. The highest degree of binding was obtained in the medial occipital cerebral cortex followed by frontal cortex, cerebellum, thalamus, striatum and pons. Two psychiatric patients with anxiety syndromes who had been treated for a long time with high doses of benzodiazepines had roughly the same degree of maximal [11C] Ro 15-1788 binding in brain regions as the healthy subjects but the rate of decline of [11C] Ro 15-1788 in the brain was higher. This indicates that there is measurable competition between [11C] Ro 15-1788 binding and clinical benzodiazepine concentrations in the body fluids of psychiatric patients. The results demonstrate that [11C] Ro 15-1788 should be a valuable tool for quantitative analyses of benzodiazepine receptor characteristics and receptor occupancy in the brain of patients with neuropsychiatric disorders.

Normal electroretinogram and no toxicity signs after chronic and acute administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole to the cynomolgus monkey (Macaca fascicularis)--a possible new treatment of methanol poisoning.

High doses of 4-methylpyrazole (4-MP) could be administered to monkeys in long- and short-term experiments without yielding any general toxicity or any toxic influence on the retinal photoreceptors, the conduction of impulses through the retina or on the activity in the inner nuclear layer detectable by recording the electroretinogram (ERG). Both series included a low dose (20 mg/kg) and a high dose level (100 mg/kg), the former being a tentative therapeutic dose. In the first series the substance was administered for 6 weeks and the toxicity regarding clinical signs, hematology and blood chemistry, and gross and microscopic pathology evaluated. Furthermore ophthalmoscopy with assessment of the fundus structures and recordings of the ERG were performed. The second series was mainly concerned with revealing of any direct effect of 4-MP on the ERG. Because of the low toxicity of 4-MP and its powerful inhibitory capacity on alcohol dehydrogenase, the substance should prove a potential tool in clinical alcohol research and an effective antidote in clinical situations where inhibition of alcohol dehydrogenase (ADH) is the key to a successful outcome of, for example, methanol and ethylene glycol poisoning.