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H Uno

Publications and source records attributed to H Uno.

At least 19 recordsLinked to original sources
PubMed1979

Studies on 3-substituted 1,2-benzisoxazole derivatives. 6. Syntheses of 3-(sulfamoylmethyl)-1,2-benzisoxazole derivatives and their anticonvulsant activities.

Several 3-(sulfamoylmethyl)-1,2-benzisoxazole derivatives were synthesized from 3-(bromomethyl)-1,2-benzisoxazole by the reaction with sodium bisulfite followed by chlorination and amination. Some of them displayed marked anticonvulsant activity in mice. The introduction of a halogen atom to the 5 position of the benzisoxazole ring caused increased activity and neurotoxicity; the substitution of a sulfamoyl group caused decreased activity. The activity of monoalkylated compounds might be the result of biotransformation. Among these compounds, 3-(sulfamoylmethyl)-1,2-benzisoxazole (1a) was thought to be the most promising as an anticonvulsant from the ratio of NTD50 and ED50.

Animals↗
PubMed1979

Synthesis of 2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole derivatives and their central nervous system activities.

The synthesis and some pharmacological effects of cis- and trans-2-substituted 2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole derivatives are described. In these derivatives, the substituents of the 2, 5 and 8 position, together with the relative configuration of the 4a and 9b position, influenced the potency of the central nervous system activities. A cis-2-[3-(p-fluorobenzoyl)propyl] analogue (5k) of carbidine (1) possessed not only thymoleptic-like biological activity but had more potent neuroleptic activity than the parent drug.

Animals↗
PubMed1978

Neural uptake of catecholamines and their molecular structures: a histopharmacologic study.

Using ultrastructural and histofluorescence methods, we investigated the uptake mechanism of catecholamines by the nerve terminals in the cutaneous smooth muscles of stump-tailed macaques (Macaca arctoides). This in vivo approach ultilized the observed cytotoxic effects of 6-hydroxydopamine on these catecholamine-containing terminals and the protective effects of simultaneous treatment with catecholamines (dopamine, norepinephrine, and epinephrine), their 3-0-methylated derivatives (metanephrine and normetanephrine), and catechol acids (3,4-dihydroxymandelic acid and 2, 4, 5-trihydroxymandelic acid). Both catecholamines and 3-0-methylated derivatives protected these nerve terminals from destruction by 6-hydroxydopamine, but catechol acids did not. However, the 3-0-methylated derivatives were less effective than the catecholamines. The degree of protection afforded by these amines depended largely on their concentration. Only catecholamines intensified the electron density of the intravesicular mass or the fluorescence in the nerve terminals; therefore, 3-0-methylated derivatives may inhibit 6-hydroxydopamine uptake at axoplasmic membrane sites, but not inside the axon. These observations led to the discovery that these are two sites for the catecholamine uptake process. One site is the axoplasmic membrane. The terminals are protected by catecholamines and their 3-0-methylated derivatives from 6-hydroxydopamine uptake and thus destruction. The other site is the intraaxonal compartments. Here competitive binding between the vesicular protein and both 6-hydroxydopamine and the catecholamines plays a main role.

Animals↗
PubMed1978

Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 2. Structure-activity relationships of 1-cycloalkyl-4-(1,2-diphenylethyl)piperazines.

Forty-six 1-cycloalkyl-4-(1,2-diphenylethyl)piperazines were synthesized. The influence of substituents on phenyl groups of 1-cycloalkyl-4-(1,2-diphenylethyl)piperazines 4a-c on the analgesic activity was investigated in experimental animals. The most active compounds, 5a-c, in this series had a m-hydroxyl group on the 2-phenyl group of 4a-c, while morphine has a phenolic hydroxyl group para to th- aminoethyl moiety. Their activities were 23-56 and 23-38 times those of their original compounds 4a-c and morphine, respectively, tested by the D'Amour-Smith method after subcutaneous administration.

Analgesics↗
PubMed1976

Catecholamine-containing nerve terminals in piloarrector muscles of stump-tailed macaques (Macaca arctoides) and the effects of local injection of 6-, and 5-hydroxydopamine.

The fluorescence histochemical method of Falck-Hillarp (62) demonstrates dense plexuses of catecholamine-containing nerves in the piloarrector muscles of adult stump-tailed macaques. When these muscle fibers are viewed under the electron microscope, most of the axon terminal profiles between them contain numerous dense-cored vesicles (adrenergic); the rest of the terminals contain mainly agranular vesicles (cholinergic). Intradermal injections of 6-hydroxydopamine (6-OHDA, 1 and 5 mg) or 5-hydroxydopamine (5-OHDA, 10mg) into the scalp caused the fluorescence from the nerve fibers in the muscles to completely disappear. The 6-OHDA injections induced severe degenerative changes in the adrenergic terminals whereas the 5-OHDA injections caused only the granules in the vesicles to increase in numbers. Thus, the piloarrector muscles of these macaques are innervated with both adrenergic and cholinergic terminals, but the former are more numerous than the latter.

Animals↗
PubMed1976

Synthesis of some 1, 8- and 2, 8-disubstituted derivatives of adenosine cyclic 3', 5'-phosphate and their interaction with some enzymes of cAMP metabolism.

1, 8-Disubstituted derivatives of adenosine cyclic 3', 5'-phosphate (cAMP) were synthesized by N-oxidation or N-methylation of previously reported 8-substituted cAMP derivatives to yield 8-bromoadenosine cyclic 3', 5'-phosphate 1-oxide and 8-(benzylthio)-1-methyladenosine cyclic 3', 5'-phosphate. Substituents were introduced into the 8 position of 2-methyladenosine cyclic 3', 5'-phosphate and 2-butyladenosine cyclic 3', 5'-phosphate by bromination, followed by treatment with sodium benzylmercaptide, sodium p-chlorothiophenolate, or, in the former case, sodium azide. Each of the 1,8- and 2,8-disubstituted derivatives of cAMP was tested as activators of cAMP-dependent protein kinase and as substrates for the inhibitors of cyclic nucleotide phosphodiesterases. Depending on the substitutions, examples were found where the disubstituted derivatives were either more active, equally as active or less active than the monosubstituted parent compounds as protein kinase activators. For the compounds reported, 8-substitution completely or substantially eliminated the ability of 1- or 2-substituted derivatives of cAMP to serve as substrates for phosphodiesterase and diminished the ability of these latter derivatives to inhibit cAMP hydrolysis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Hydatid disease in four nonhuman primates.

Hydatid disease was detected in 4 nonhuman primates (Galago crassicaudatus, Lemur catta, and 2 Macaca mulatta) at the Oregon Regional Primate Research Center. Involvement extended from 2 1/2 to 7 1/2 years. A 6-cm cyst was surgically removed from the thoracic cavity of 1 macaque; 6 years later multiple cysts were found in its abdominal cavity. Lesions found in the primates at necropsy included compression or displacement of the lungs, hydroureter and hydronephrosis, and distension of the abdomen--all related to impingement of developing cysts.

Abdomen↗
PubMed1975

2-substituted derivatives of adenosine and inosine cyclic 3',5'-phosphate. Synthesis, enzymic activity, and analysis of the structural requirements of the binding locale of the 2-substituent on bovine brain protein kinase.

A number of 2-substituted cyclic nucleotide derivatives were synthesized and investigated as activators of cAMP-dependent protein kinase and as substrates for and inhibitors of cAMP phosphodiesterase. Ring closure of 5-amino-1-beta-D-ribofuranosylimidazol-4-carboxamide cyclic 3',5'-phosphate (1) with various aldehydes according to a new procedure (Meyer, R. B., Jr., Shuman, D.A., and Robins, R. K. (1974), J. Am. Chem. Soc. 96, 4962) gave new derivatives of adenosine cyclic 3',5'-phosphate with the following 2-substituents: n-propyl, n-hexl, n-octyl, n-decyl, styryl, o-methoxyphenyl, and 2-thienyl. Alkylation of 2-mercaptoadenosine cyclic 3',5'-phosphate (20, Meyer et al., 1974) gave new cAMP derivatives with the following 2-substituent: ethylthio, n-propylthio, isopropylthio, allylthio, n-decylthio, and benzylthio. Deamination of 2-methyl-,2-n-butyl-, and 2-ethylthioadenosine cyclic 3',5'-phosphate. Using multiple regression analysis, a striking relationship was found between the relative potency of the compounds as activators of bovine brain cAMP-dependent protein kinase and parameters describing the hydrophobic, steric, and electronic character of the substituents on these compounds. All compounds were substrates for a cyclic nucleotide phosphodiesterase preparation from rabbit kidney. Additionally, the compounds were as a group, good inhibitors of the hydrolysis of cAMP by phosphodiesterase preparations from rabbit lung, beef heart, and dog heart.

Animals↗
PubMed1975

Catecholamine-containing nerve terminals of the eccrine sweat glands of macaques.

The external layer of the median eminence (ELME) and the arculate nucleus of male rats were studied with the Falck-Hillarp technique and electron microscopy of aldehyde-OsO4 or KMnO4 fixed after various types of hypothalamic deafferentation experiments with the Halász knife. Special reference was paid to the monoamine systems and the results can be summarized as follows. 1. The main monoaminergic input to the ELME comes from the arcuate nucleus-periventricular area via a dorsal approach. A horizontal transection through the arcuate nucleus decreases the percentage of monoamine boutons i.e. boutons with small granular vesicles, from 31.6% in the controls to 4.4% in the lesion group, whereas only a small effect is seen after anterior (or complete) deafferentations. 2. A major input to the ELME enters the basal hypothalamus at the anterior-lateral aspects (see Réthelyi and Halász, 1970). The fibers cut after anterior deafferentations in all probability mainly come from cell bodies localized in the anterior hypothalamus or even further rostrally but some may represent NA axons ascending from the lower brain stem. 3. The degeneration course of nerve endings in the ELME both after anterior deafferentations as well as after lesions in the arcuate nucleus is rapid (within 2-3 days) and morphologically characterized by an initial aggregation of large dense cored vesicles seemingly to electron dense bodies within the boutons and probably also to a closer spacing of the small electron lucent synaptic vesicles (see Raisman, 1972). This type of degeneration seems to take place both in monoamine and non-monoamine neurons. 4. Degenerating boutons are found in the arcuate nucleus after anterior and complete deafferentations. Thus, the anterior hypothalamus may exert an "indirect" control of the pituitary gland via synapses on arcuate neurons although quantitatively the "direct" influence through the projection to the ELME is of more importance. 5. After anterior deafferentations enlarged axons containing large amounts of large dense cored vesicles and other organelles are found caudally of the cut indicating the existence of rostral projections from the medial hypothalamus.

Animals↗
PubMed1975

Radiographic approach to stereotaxic surgery in rhesus monkeys.

A method is described which uses radiographic techniques to identify ventricular and bony landmarks as guides in placing probes into specific areas of the brain in the rhesus monkey. This approach requires a relatively simple modification of a standard stereotaxic instrument and is applicable to various physiological and behavioral experiments in species where cranial variability limits the accuracy of stereotaxic surgery.

Animals↗