Showing papers by "Eli Lilly and Company published in 1974"
TL;DR: Lilly 110140 is a highly selective inhibitor of serotonin uptake into synaptosomes of rat brain, unlike previous monoamine uptake inhibitors that also inhibit the uptake of norepinephrine and dopamine.
438 citations
TL;DR: In all cases rat hypothalamic extracts significantly inhibited pituitary prolactin (PRL) release in vitro and the catecholamine containing acid eluate from the alumina adsorption procedure was able to inhibit PRL release to the same degree as untreated hypothalamic extract.
Abstract: Rat hypothalamic extracts, dopamine (DA), norepinephrine (NE), and epinephrine (EP), were incubated with rat pituitary tissue in medium 199. In all cases rat hypothalamic extracts significantly inhibited pituitary prolactin (PRL) release in vitro. When the hypothalamic extracts were subjected to preincubation with a rat brain monoamine oxidase enzyme preparation (MAO) or ot aluminum oxide (alumina) catecholamine adsorption, the hypothalamic extracts lost their ability to inhibit PRL release in vitro Pepsin pretreatment did not impair the inhibition of PRL release by hypothalamic extracts and iproniazid 10 μg/ml of medium blocked the effect of MAO on the hypothalamic extracts. The DA and NE content of MAO treated and untreated hypothalamic extracts was measured by a fluorometric technique. The catecholamine containing acid eluate from the alumina adsorption procedure was able to inhibit PRL release to the same degree as untreated hypothalamic extracts. Dopamine (5.26 × 10−9 to 5.26 × 10−7M) and NE (2.42 × ...
255 citations
TL;DR: Lilly 110140 had no effect on brain levels of tryptophan, serotonin, dopamine, or norepinephrine, but it decreased 5-hydroxyindoleacetic acid (5HIAA) levels, and reduced turnover was indicated by a decreased rate of fall in brain serotonin levels after p-chlorophenylalamine was given to inhibit serotonin synthesis.
197 citations
TL;DR: The results imply that the dopamine receptor that inhibits prolactin release may be similar to the dopamine receptors involved in the action of antipsychotic drugs.
Abstract: Antipsychotic drugs have been found to markedly stimulate prolactin secretion in male and female rats. The amount of prolactin released was greater in females than in males. Most non-antipsychotic phenothiazines failed to alter prolactin. These results imply that the dopamine receptor that inhibits prolactin release may be similar to the dopamine receptor involved in the action of antipsychotic drugs.
117 citations
TL;DR: It is demonstrated that dopamine receptor stimulation results in inhibition of prolactin secretion in vivo, and pimozide, a specific dopamine antagonist, was able to reduce the amount of prolACTin released by the pituitary tissue.
Abstract: Studies were performed to determine if apomorphine (APO), a specific dopamine receptor stimulant, was able to influence serum prolactin levels in vivo and in vitro. Administration of APO (ip, 20 mg/kg) to rats with normal 4-day estrous cycles reduced serum prolactin levels during diestrus and prevented the proestrous rise of serum prolactin. The elevation of serum prolactin observed after chlorpromazine treatment (2.5 or 1 /mg) was significantly attenuated by APO. In addition, treatment: of lactating rats with 15 mg/kg of APO prevented the suckling-induced rise of serum prolactin. These observations demonstrate that dopamine receptor stimulation results in inhibition of prolactin secretion in vivo. Incubation of pituitary halves in vitro with 8 + 10−8M (25 ng/ml) APO consistently resulted in a significant decrease in the amount of prolactin released by the pituitary tissue. Concentrations of APO as low as 1.6 + 10−8M (5 ng/ml) were effective.Pimozide, a specific dopamine antagonist, was able to reduce the...
90 citations
72 citations
TL;DR: Interestingly, a number of simple ergot molecules lacking the peptide side chain are able to inhibit prolactin, and dose-response studies show that minute amounts of an ergot can cause a significant reduction in Prolactin secretion.
Abstract: Peptide-containing ergot alkaloids and synthetic ergoline derivatives were administered to reserpine-treated male rats in order to evaluate their prolactin-inhibiting properties. Each compound was administered ip at a standard 50 ¼g/kg dose. The 9,10-dihydrogenated ergots, dihydroergocornine, and dihydroergocryptine were able to inhibit prolactin to the same degree as ergocornine and ergocryptine. This is significant because the 9,10-dihydrogenation process removes the toxic vasoconstrictive properties from the molecule and allows the prolactin-inhibiting ability to remain intact. In addition, dose-response studies show that minute amounts of an ergot can cause a significant reduction in prolactin secretion. The failure of ergocorninine to inhibit prolactin secretion demonstrates that the stereochemical configuration of the molecule at the 8 position is important for prolactin-inhibiting ability. Interestingly, a number of simple ergot molecules lacking the peptide side chain are able to inhibit prolactin...
61 citations
01 Jan 1974
TL;DR: In this article, a method described in a previous paper has been applied to the calculation of hydrophobic interactions between hydrocarbon pairs and aggregates, finding that a small barrier is found at a distance of less than a water molecule diameter.
Abstract: A method described in a previous paper has been applied here to the calculation of hydrophobic interactions between hydrocarbon pairs and aggregates. Generally a small barrier is found at a distance of less than a water molecule diameter. At minimal contact between hydrocarbon pairs, there is little or no binding energy. Two hydrocarbon chains may be arranged side by side in such a fashion so that binding is substantial, having a maximum upper limit of — 800 cal per ethylene unit pairs. As molecules aggregate binding increases. A model receptor may be constructed by arranging several hydrocarbon chains to form a cleft. The hydrophobic binding between such a cleft and a molecule of ethane is found to be about —2.5 kcal.
60 citations
Patent•
11 Jan 1974TL;DR: A child-resistant blister package with a receptacle formed from a stiff flexible sheet material having a flange extending about it and adhered to a cover sheet is described in this article.
Abstract: A child-resistant blister package with a receptacle formed from a stiff flexible sheet material having a flange extending about it and adhered to a cover sheet. The flange has a transverse arched portion that is spaced in a non-adherent relationship with the cover sheet which in turn has a weakened and rupturable portion in alignment with the arched portion of the flange. The arched portion of the flange is expandable and enables one to rupture the weakened portion of the cover sheet by stretching or pulling the blister package, thereby enabling one to pull off the remainder of the cover sheet.
55 citations
TL;DR: Results indicate that prolactin can cross the blood-brain barrier and appear in CSF in quantities that may be sufficient to exert behavioral or short loop feedback effects.
Abstract: Studies were performed to determine if prolactin appears in cerebro-spinal fluid (CSF) after intravenous administration to rabbits and if prolactin is a normal constituent of CSF in rats. Intravenous administration of a rat pituitary homogenate containing 250 μg of prolactin to adult female New Zeland white rabbits resulted in the appearance of significant quantities of prolactin in the CSF. In rats prolactin was almost undetectable in CSF on diestrous day 2, but significant quantities of prolactin were present in the CSF on the afternoon of proestrus. These results indicate that prolactin can cross the blood-brain barrier and appear in CSF in quantities that may be sufficient to exert behavioral or short loop feedback effects.
55 citations
TL;DR: The ability of 3-triflouromethylphenoxy)-N-methyl-3-phenylpropylamine amine hydrochloride and chlorimipramine to block uptake into serotoninergic and noradrenergic neurons was determined by their antagonism of serotonin depletion in brain by p-chloroamphetamine and norephrine depletion in heart by 6-hydroxydopamine.
Patent•
02 Dec 1974TL;DR: In this article, an automatic sampler-injector for use in liquid chromatographic analytical procedures is described which comprises in combination, a cylinder closed on one end, and a stopper for said cylinder, said stopper having an outside diameter slightly greater than the inside diameter of said cylinder and adapted for insertion in the open end thereof.
Abstract: An automatic sampler-injector for use in liquid chromatographic analytical procedures is described which comprises in combination, A: (1) a cylinder closed on one end, and (2) a stopper for said cylinder, said stopper having an outside diameter slightly greater than the inside diameter of said cylinder and adapted for insertion in the open end thereof; and B: (1) a means for positioning said cylinder with said stopper in place therein beneath the point of a hollow needle, (2) an annular collar disposed around said needle at a sufficient distance from the point thereof to permit said point to penetrate said stopper, said collar having an outside diameter less than the inside diameter of said cylinder, (3) means for reciprocally moving said needle down and up in a vertical plane, (4) a conduit leading from said needle to a multiple inlet port valving means having a core with passageways communicating with said ports, (5) a closed sampling loop connected to two ports of said valving means, (6) means adapted to automatically position said valving means so that said sampling loop can first receive a sample for injection into a liquid chromatographic column and second to discharge such a sample into said chromatograph, and (7) means to effect the discharge of the contents of said sampling loop into said liquid chromatographic column.
Patent•
01 Apr 1974TL;DR: In this article, the Alpha -Aminoacyl-3-halo cephalosporins represented by the formula where R is phenyl, substituted phenyl or furyl; X is fluoro, chloro, bromo or iodo and the non-toxic pharmaceutically acceptable salts thereof are valuable, orally effective antibiotics.
Abstract: Alpha -Aminoacyl-3-halo cephalosporins represented by the formula WHEREIN R is phenyl, substituted phenyl, thienyl or furyl; and X is fluoro, chloro, bromo or iodo and the non-toxic pharmaceutically acceptable salts thereof are valuable, orally effective antibiotics.
TL;DR: The capacity of the brain to synthesize 5-hydroxyindoles, as indicated by the increases in serotonin and 5-Hydroxyindoleacetic acid after the injection of various doses of l -tryptophan, was not altered.
Patent•
12 Apr 1974TL;DR: In this paper, 5-(2-Aminophenyl)pyrazole-3-carboxylic acids, useful as intermediates in the preparation of compounds useful as complement inhibitors, are prepared by reacting a 2-nitroacetophenone with a dialkyl oxalate in the presence of a strong base and in an inert solvent.
Abstract: 5-(2-Aminophenyl)pyrazole-3-carboxylic acids, useful as intermediates in the preparation of compounds useful as complement inhibitors, are prepared by reacting a 2-nitroacetophenone with a dialkyl oxalate in the presence of a strong base and in an inert solvent to give the corresponding alkyl 2-nitrobenzoylpyruvate, condensing the alkyl 2-nitrobenzoylpyruvate with hydrazine in an inert solvent to give an alkyl 5-(2-nitrophenyl)-pyrazole-3-carboxylate, reducing the nitro group catalytically to give the alkyl 5-(2-aminophenyl)pyrazole-3-carboxylate, and, if desired, hydrolyzing the ester to the free acid.
TL;DR: A group of epipolythiopiperazinedione antibiotics obtained from the fermentation broth of Penicillium turbatum and the fermentation, isolation, biological properties and structure elucidation of three metabolites of this group are discussed.
Abstract: A group of epipolythiopiperazinedione antibiotics was obtained from the fermentation broth of Penicillium turbatum. The fermentation, isolation, biological properties and structure elucidation of three metabolites of this group are discussed.
TL;DR: The results make it seem unlikely that 4-chloroamphetamine's depletion of brain serotonin and 5-hydroxyindoleacetic acid is mediated by the conversion of 4- chloroamphetamine to these metabolites.
TL;DR: Kinetic studies indicated that inhibition by fenoprofen was competitive while that of indomethacin was non-competitive, which indicates that inhibition of prostaglandin synthesis at physiological substrate concentration is competitive.
TL;DR: The long duration of action of LAM as an opiate substitute is most likely due to the conversion to its metabolites.
Patent•
26 Dec 1974TL;DR: In this article, a method of controlling aquatic weeds which comprises adding to a body of water containing the aquatic weeds a substituted 1-thiadiazolyl-3-arylurea in sufficient quantity to kill the weeds.
Abstract: A method of controlling aquatic weeds which comprises adding to a body of water containing the aquatic weeds a substituted 1-thiadiazolyl-3-arylurea in sufficient quantity to kill the weeds.
Patent•
15 Oct 1974
TL;DR: In this article, a focused, ultra short-pulsed laser beam was used to kill microorganisms in the inside of a container comprising repeatedly sparking a focused and ultra short pulsed beam.
Abstract: Novel method of killing microorganisms in the inside of a container comprising repeatedly sparking a focused, ultra-short-pulsed laser beam in the inside thereof.
Patent•
19 Dec 1974TL;DR: Prolactin secretion is inhibited by administering a 6methyl-8 alpha -(N-acyl)amino-9-ergolene as mentioned in this paper, which is a 6-methyl 8 alpha -amino 9-ergoline.
Abstract: Prolactin secretion is inhibited by administering a 6-methyl-8 alpha -(N-acyl)amino-9-ergolene.
Patent•
03 Jul 1974TL;DR: In this article, a plasminogen activator is used to produce mammalian tissue cells in an aqueous nutrient culture medium until cells have attained development to confluency or maximum population density.
Abstract: Enhanced plasminogen activator yields are obtained by culturing plasminogen activator producing mammalian tissue cells in an aqueous nutrient culture medium until cells have attained development to confluency or maximum population density; continuing incubation in the presence of an antimitotic agent, e.g., podophylotoxin, colchicine and derivatives thereof, vincristine, vinblastine and derivatives thereof; recovering the activator from the separated aqueous culture medium by adsorption on hydroxyapatite and elution therefrom; and purifying the activator via salt precipitation followed by DEAE cellulose chromatography and gel filtration chromatography. Plasminogen activator is provided in clinically useful amounts for treatment of thromboembolic conditions.
TL;DR: The db/ db mice seem to be different from ob/ob mice in their greater sensitivity to cold stress and to heat stress and their lesser sensitivity to hypothermie drugs; this difference may suggest a specific thermoregulatory defect in the db/db mice.
TL;DR: Phenylethanolamine N-methyl transferase catalyzes the methylation of norepinephrine, forming epinephrine in the adrenal medulla, and is inhibited by phenethylamines and other compounds structurally similar to its substrates, as well as by agents that bind to sulfhydryl groups.
TL;DR: Six healthy male subjects were given 0.5 mg of digoxin on three separate occasions in the form of an elixir and two different commercially available brands of compressed tablets, and the two tablets showed nearly identical blood levels and relative bioavailabilities.
Patent•
17 Jan 1974TL;DR: In this article, a submerged aerobic culture of Streptomyces chartreusis NRRL 3882 was used to produce antibiotic A23187, which demonstrates antimicrobial activity and exhibits ionophorous properties, with a specificity for divalent cations.
Abstract: Antibiotic A23187 and process for production thereof by submerged aerobic culture of Streptomyces chartreusis NRRL 3882. The antibiotic demonstrates antimicrobial activity and exhibits ionophorous properties, with a specificity for divalent cations.
Patent•
13 May 1974TL;DR: There are disclosed novel 3-(5-nitro-2-imidazolyl)-pyrazoles exhibiting utility as antibacterial, antiprotozoal and antifungal agents, making the compounds useful particularly in veterinary medicine, especially in controlling bacterial and protozoal infections of poultry and swine as discussed by the authors.
Abstract: There are disclosed novel 3-(5-nitro-2-imidazolyl)-pyrazoles exhibiting utility as antibacterial, antiprotozoal, and antifungal agents, making the compounds useful particularly in veterinary medicine, especially in controlling bacterial and protozoal infections of poultry and swine. The compounds are also active as growth promoters in chickens.
TL;DR: Erythromycin synthesis was markedly impaired in submerged cultures under high carbon dioxide tensions, while growth of Streptomyces erythreus was unaltered by increased carbon dioxide.
Abstract: Erythromycin synthesis was markedly impaired in submerged cultures under high carbon dioxide tensions. Growth of Streptomyces erythreus , however, was unaltered by increased carbon dioxide.