A hypothesis that the β-adrenergic blocking drugs may possess weak α-adrenergic blocking activity, and that their antihypertensive effect may be due to this combined α- and β-adrenergic blockade was tested. Phenoxybenzamine (PBZ) and propranolol (PPL) were selected as α- and β-blocking drugs, respectively. They were given orally at doses of 1-100 mg/kg per day, 5 days per week. Their combined antihypertensive effects were determined in spontaneously hypertensive ; deoxycorticosterone and salt hypertensive ; and two kidney, one clip renal hypertensive rats. PBZ treatment showed antihypertensive effect in three models of hypertensive rats. However, addition of PPL either did not affect or rather antagonized the effect of PBZ. Moreover, the combined treatment increased side-effects, typically seen as urinary incontinence. The results did not support the above hypothesis, at least when the blockade was caused with PBZ and PPL.

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When anesthetized rats were exposed to microwave (power output 1.3 kw, frequency 2, 450 MHz), the cyclic AMP phosphodiesterase activity showed a rapid decline in the skeletal muscle, heart, trachea and lung ; no activity essentially could be detected after a 30 sec irradiation. Cyclic AMP levels in these tissues also decreased rapidly to constant values within 30 sec. Concentrations of cyclic AMP in the heart, skeletal muscle, trachea and lung measured by the tissue fixation with liquid nitrogen were approximately 3, 3, 4 and 4 times higher than those after microwave irradiation, respectively. The intravenous injection of procaterol (1 μmol/kg), aβ₂-adrenoceptor agonist, caused a 6-fold increase in the trachea cyclic AMP level when measured after microwave fixation but only a 2-fold increase when measured after liquid nitrogen fixation. It is concluded that rapid tissue fixation by microwave irradiation may provide a useful means for obtaining reliable values of the tissue cyclic AMP content.

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Among the various kinds of spices tested, the aqueous extracts of dill weed from Anethum graveolens L. and dill seeds from A. sowa D.C. (Umbelliferae), exhibited a mutagenicity to Salmonella typhimurium, strains TA98 and TA100. The aqueous methanol extracts were fractionated by the mutation assay using the strain TA98 with S-9 Mix. Isorhamnetin 3-sulfate (persicarin) and quercetin 3-sulfate were characterized as the mutagenic principles. Carcinogenicity was not observed for dill weed and seeds when the diets containing these in 33% were administered for 450 and 410 days, respectively, to the inbred strain ACI rats.

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The emotional transmission was studied in olfactory bulbectomized mice by the communication box method using methamphetamine toxicity (mortality) as the index. Intraperitoneal administration of methamphetamine 15 mg/kg in the sender, responder and control groups of olfactory bulbectomized mice resulted in a marked rise of mortality in the sender and responder groups, compared to the control group. In the sham-operated mice, on the other hand, the mortality markedly rose in the sender group, but the mortality of the responder group was lower than that of the sender group, and was higher than that of the control group. As the result of studies on the emotional transmission using methamphetamine toxicity, the emotional reaction in the sender group appears to be transmitted to the responder group in olfactory bulbectomized animals.

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A radioimmunoassay has been developed which enables accurate determination of haloperidol in human serum. Antiserum was prepared by immunizing guinea pigs with haloperidol (O-carboxymethyl) oxime derivative (III) coupled with bovine serum albumin. With the antiserum, ³H-haloperidol and dextran-coated charcoal, the assay of haloperidol in serum was possible over a concentration range of 1 to 50 ng/ml, using 0.1 ml of human serum without the need of an extraction procedure. Data obtained by radioimmunoassay are in good agreement with those obtained by gas chromatography. No appreciable cross-reactivity was observed neither with haloperidol metabolites nor with other butyrophenone neuroleptics. Serum levels of haloperidol in schizophrenic patients receiving single oral dosing (6 mg/subject) have also been determined.

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The effect of captopril (D-3-mercapto-2-methylpropanoyl-L-proline), a converting enzyme inhibitor, on the systemic blood pressure in pentobarbital anesthetized rats was investigated. Experiments were performed in four groups of rats : untreated, Na-restricted, furosemide treated and bilaterally nephrectomized, respectively. Intravenous injection of 1 mg/kg of captopril caused a significant hypotensive effect in the three groups of rats but not in the nephrectomized group. Individual values for the hypotensive effect produced by captopril and plasma renin activity obtained just before injection of captopril showed a highly significant correlation.

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Effect of diisopropyl 1, 3-dithiol-2-ylidenemalonate (NKK-105) on the components of rat liver microsomal electron transport system was investigated by comparison with those of phenobarbital, 3-methylcholanthrene and polychlorinated biphenyl. When NKK-105 was administered to rats at a dose of 250 mg/kg/day for 7 days, cytochrome b₅ content and NADPH-cytochrome c reductase activity were significantly increased but cytochrome P-450 content to the lesser extent. Three inducers of the drug metabolizing enzymes remarkably increased cytochrome P-450 content but increased cytochrome b₅ content to a lesser extent.

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Magnetic guidance of magnetic albumin microsphere for site specific drug delivery was investigated in vivo. After intravenous injection in mice, magnetic microspheres localized in the site (lung) at which two permanent magnets were placed. Injection into the renal artery in rats also indicated that the microspheres were concentrated at the kidney by a magnetic field. When magnet was not applied, however, the microspheres were concentrated mainly in the liver. Such preferential localization by magnetic means suggested that magnetic albumin microspheres could become effective drug carriers with site specificity for the delivery of chemotherapeutic agents in cancer therapy.

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