An attempt was made to postpone term in 59 pregnant rats by s.c. injections of indomethacin or cyproheptadine, or a combination of both. The cyproheptadine group gave birth to their litters on days 20-22, yet indomethacin postponed labour to the 23rd day, both when given alone or in combination with cyproheptadine. As the fourth saline group went into labour on the 20--23rd day the indomethacin postponement cannot be considered significant. Indomethacin being a prostaglandin antagonist and cyproheptadine a serotinin antagonist, it may be concluded that neither prostaglandin nor serotonin are decisive for the intricate process which triggers parturition. Other factors, such as decrease of progesterone, increase of oestrogen and perhaps foetal oxytocin, as well as placental ACTH, seem to concur in inducing labour, their effect being fortified by serotonin and prostaglandins during parturition.

Exposure of adult male rats to continuously elevated temperature of 32-34 degrees C caused a significant decrease of HIOMT activity involved in the specific metabolic process of production of melatonin, considered an active pineal hormone. The effect was already evident after 24 h exposure and increased further during the next 48 h. The results obtained substantiate previous data that the pineal gland may be involved in the system regulating adaptation to extreme temperature changes.

SummaryA single intramuscular injection of the sodium succinate ester of chloramphenicol (50 mg./kg.) produced in serum of dairy cows peak drug levels which were six times higher than after an equivalent dose of chloramphenicol dissolved in acetyl dimethylamine‐propylene glycol. The ester, however, was eliminated much faster from serum.Three 50 mg./kg. intramuscular injections of chloramphenicol, given at 24 hour intervals, yielded progressively increasing drug concentrations in serum. Drug levels in milk from chronically but subclinically infected glands of cows and ewes amounted, on the average, to 50 % of the corresponding serum concentrations and were not influenced by the pH of milk. During the course of acute mastitis the concentrations of chloramphenicol in the secretions were only slightly higher than in milk collected from the normal glands of the same cows but the milk/serum ultrafiltrate ratios were always near 1.0.Chloramphenicol apparently penetrated into milk by non‐ionic passive diffusion. Circumstantial evidence is presented that neither the unhydrolyzed ester nor the metabolites of chloramphenicol diffused readily into milk.ZusammenfassungChloramphenicol‐Konzentrationen im Blut und in der Milch bei gesunden und mastitiskranken Kühen und Schafen nach intramuskulärer Verabreichung von Chloramphenicol und Chloramphenicol‐Natrium‐SuccinatEine einmalige intramuskuläre Injektion von Chloramphenicol‐Natrium‐Succinat (50 mg/kg) bewirkten im Serum von Milchkühen eine 6mal höhere Konzentration des Medikamentes als eine äquivalente Dosis von Chloramphenicol, welche in Acetyl‐Dimethylamin‐Propylen‐Glycol gelöst war. Das zuerst erwähnte Esterpräparat wurde allerdings schneller aus dem Serum eliminiert. Die 3malige intramuskuläre Injektion von Chloramphenicol (50 mg/kg) in Intervallen von 24 Stunden hatte eine sukzessive Erhöhung der Konzentration des Medikamentes im Serum zur Folge. Die Konzentrationen des Medikamentes in der Milch von Kühen und Schafen, welche mit chronischen, jedoch subklinischen Mastitiden behaftet waren, betrugen im Mittel bis zu 50 % der entsprechenden Serumkonzentrationen und wurden vom pH der Milch nicht beeinflußt.Bei Tieren mit einer akuten Mastitis waren die Chloramphenicol‐Konzentrationen nur wenig höher als in der Milch normaler Euterviertel der gleichen Tiere.Die Chloramphenicol‐Konzentrationsverhältnisse zwischen Milch und Serumultrafiltrat betrugen immer ungefähr 1. Das Chloramphenicol scheint durch passive, nicht‐ionische Diffusion in die Milch zu gelangen.Weder der unhydrolysierte Ester noch die Metaboliten des Chloramphenicol diffundieren leicht in die Milch.RésuméConcentration du chloramphénicol dans le sang et le lait chez des vaches et des brebis normales et atteintes de mastite après application intramusculaire de chloramphénicol et de chloramphénicol‐succinate de sodiumUne injection intramusculaire unique de l'ester de chloramphénicolsuccinate de sodium (50 mg/kg) produit, dans le sérum des vaches laitières, des taux de médicament six fois plus élevés que la dose équivalente de chloramphénicol dissout dans l'acétyl‐diméthylamine‐propylène glycol. L'ester est par contre éliminé plus rapidement du sérum.Trois injections intramusculaires de chloramphénicol (50 mg/kg), à 24 heures d'intervalle, donnent une augmentation progressive de la concentration du médicament dans le sérum. La concentration du médicament dans le lait des vaches et des brebis infectées chroniquement, mais de manière sub‐clinique, atteint en moyenne 50 % de la concentration sérique correspondante et n'est pas influencée par le pH du lait. Chez les animaux atteints d'une mastide aiguë, les concentrations du chloramphénicol dans les sécrétions lactées ne sont que légèrement plus élevées que dans le lait des quartiers sains des mêmes vaches, mais le rapport des concentrations entre les ultra‐filtrats lait/sérum est toujours près de 1.0.Le chloramphénicol pénètre dans le lait par diffusion passive nonionique. Il est évident que ni l'ester non hydrolysé, ni les métabolites du chloramphénicol ne diffusent aisément dans le lait.ResumenNiveles de cloramfenicol en sangre y leche en vacas normales y en las mismas y ovejas con mamitis tras la administración intramuscular de cloramfenicol y succinato sódico de cloramfenicolLa inyección intramuscular única de succinato sódico de cloramfenicol (50 mg/kg) produce en el suero sanguíneo de vacas lecheras una concentración 6 veces mayor del medicamento que una dosis equivalente de cloramfenicol, que se hallaba disuelto en acetil‐dimentilamino‐propilenglicol. Sin embargo, la especialidad ester mencionada en primer lugar se eliminaba mucho más deprisa del suero sanguíneo.Tres inyecciones intramusculares de cloramfenicol (50 mg/kg) dadas en intervalos de 24 horas producían un aumento progresivo de la concentración del medicamento en el suero. Los niveles de la especialidad en la leche de glándulas de vacas y ovejas que padecían mastitis crónicas, aunque subclínicas, ascendían como media hasta el 50 % de las concentraciones séricas correspondientes y no eran influídos por el pH de la leche.En los animales con mastitis aguda solo eran las concentraciones de cloramfenicol en las secreciones un poco mayores que en la leche recogida de los cuarterones normales de los propios animales. Las relaciones de concentración de cloramfenicol entre la leche y el ultrafiltrado sérico eran casi siempre del orden de 1,0. El cloramfenicol parece penetrar en la leche por difusión pasiva, no iónica.Ni el ester no hidrolizado ni los metabolites del cloramfenicol difunden a la leche con facilidad.

Invitro experiments with strips of pregnant rat uterus, normal estrogen-primed rat uterus and duodenum showed that cyproheptadine HCl (Periactin®), a serotonin antagonist, inhibits the intensity of spontaneous contractions of these muscle strips. The degree of inhibition depends upon the concentration of cyproheptadine. Contraction frequency was also reduced in these smooth muscles, the basic tonus not being affected. Addition of serotonin (5-HT) to the water bath increases the intensity of muscle contractions. Cyproheptadine inhibits this increase at smaller doses than those required for inhibiting spontaneous contractions. Whereas cyproheptadine does not inhibit completely the pace-maker rhythm of the muscle cells, it suppresses the amplitude of their contractions.

The pharmacokinetics of benzylpenicillin, phenoxymethyl penicillin, ampicillin, cloxacillin, penethamate hydroiodide, cephaloridine, and cephaloglycin were evaluated in lactating cows and ewes, using the 2-compartment open system model. Drug penetration into milk was studied after single intravenous (i.v.) or intramuscular (i.m.) administration and under equilibrium. Ampicillin occupied the largest relative distribution volume, and cephaloglycin the next largest; the smallest distribution volumes were obtained for benzylpenicillin, phenoxymethyl penicillin, and cloxacillin. With weakly acidic drugs, a high distribution volume was associated with a high ratio of the total drug areas of the time- concentration curve (act) in milk to the total drug act in serum and with a short appearance time in milk after i.v. administration. These antibiotics seemed to penetrate from blood to milk by nonionic diffusion, the weakly basic penethamate penetrating in the greatest proportion. Differences among the acidic drugs regarding their pentration into milk were mainly due to different pKa values.

Radioactivity distribution was determined in serum and milk of lactating ewes after parenteral administration of five labeled antibiotics: 14 C-benzylpenicillin G, 3 H-dihydrostreptomycin, 3 H-tetracycline, 14 C-chloramphenicol, and 14 C-spiramycin. Antibiotic levels were measured simultaneously by microbiological assay. Radiochemical and microbiological assay procedures presented similar kinetic patterns for uptake in serum and penetration into milk, except for tetracycline. Small reductions in milk pH markedly increased the excretion of spiramycin and slightly influenced the milk passage of penicillin, dihydrostreptomycin, and tetracycline but did not alter the transfer of chloramphenicol into milk. Thus, it appears that the five antibiotics penetrate milk in accordance with the nonionic passive diffusion principle, and that good agreement is achieved between the calculated and observed milk/serum ultrafiltrate concentration ratios obtained during equilibrium.

Haloperidol causes mammary development in rats (Mishkinsky, Khazen, Givant, Dikstein & Sulman, 1969) and ewes (Morag, Shani, Sulman & Yagil, 1971) by depression of the prolactin-inhibiting factor (Meites, 1970; Sulman, 1970). We examined whether haloperidol could elicit prolactin release in a lactating farm animal, as was demonstrated in the rat (Dickerman, Clark, Dickerman & Meites, 1972), and whether such a release would be associated with enhanced milk secretion. The effect of haloperidol on milk yield and on serum prolactin was determined in 20 lactating Awassi dairy ewes, 3 months post partum. The ewes were machinemilked twice daily at 06.00 and 17.00 h. They were then allocated at random to one of two treatment sequences, ABAB or BABA, each consisting of four 10-day periods. During the first 5 days of each period, the ewes received daily i.v. injections of 0·1 mg haloperidol/kg (A) or of its solvent (B) 30 min after