Effects of tripelennamine, N, dibenzylethylenediamine (DBED) and N, N-dibenzyl-N', N'-dimethyl-1, 2-propanediamine (DBPD) on the isotonic contractions of isolated vas deferens of guinea pig were examined. Tripelennamine and DBED potentiated the contractile responses to acetylcholine and potassium chloride in Ca²⁺-free Tyrode solution. DBPD potentiated the contractile responses to lower concentrations of acetylcholine in Ca²⁺-free Tyrode solution, but did not affect contractions induced by potassium and higher concentrations of acetylcholine in Ca²⁺-free Tyrode solution. In depolarized vas deferens, tripelennamine and DBED augmented the maximum response to Ca²⁺, while DBPD did not affect the maximum, response to Ca²⁺ and decrease the sensitivity to Ca²⁺. The contractile responses to acetylcholine in standard Tyrode solution were attenuated by lanthanum chloride and the residual contractions were not affected by tripelennamine, DBED and DBPD or decreased by DBPD. The contractile responses to potassium chloride were completely abolished by lanthanum chloride. The half-time of decrease in acetylcholine-contraction in Ca²⁺-free Tyrode solution was significantly different from that of potassium-contraction in Ca²⁺-free Tyrode solution. The contractile response of the glycerinated muscle piece of vas deferens to calcium chloride was potentiated by DBED but was not affected by tripelennamine and DBPD. These results suggest that tripelennamine and DBED facilitate nonselectively the transmembrane influx of calcium from extracellular fluid and supperficial calcium-binding sites. In addition, DBED increases the sensitivity of contractile element to cytoplasmic free calcium ion. DBPD potentiates the contractile response without affecting the transmembrane mobilization of Ca²⁺ induced by excitaion of cell membrane.

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The effect of a new aspirin derivative, aspirin-isopropylantipyrine (AIA), with potent platelet anti-aggregant activity, on several experimental thromboses was evaluated and compared with that of aspirin. AIA (50 mg./kg, s.c.) as well as aspirin (50 mg/kg, s.c.) significantly inhibited thrombus formation in extracorporeal shunt model of rats. AIA (50 mg/kg, s.c.) significantly shortened the duration of apnea and respiratory distress induced by a rapid injection of adenosine 5'-diphosphate in rats, while aspirin (50 mg/kg, s.c.) did not. Inhibitory effect of AIA (50 mg/kg, s.c.) on arachidonic acid-induced mortality in mice was less than that of aspirin (50 mg/kg, s.c.). AIA ang aspirin (10 mg/kg/d×10, s.c.) had no effect on laurate-induced arterial occlusive disease in rats. AIA (200 μM) showed weak and reversible inhibition of prostaglandin I₂ generation in isolated rat aorta strip, while aspirin (200 μM) showed irreversible inhibition. AIA (50 and 200 μM inhibited Ca²⁺-, K⁺-or norepinephrine-induced contraction on isolated rat aorta strip. AIA (200 μM) had no effect on malondialdehyde formation, cyclic AMP level and adenylate cyclase activity in rat plateless. AIA (100 μM) inhibited arachidonic acid-induced contraction on rat fundus strip by about 50%, while aspirin (100 μM) did not. These results strongly suggest that anti-thrombotic activity of AIA was originated at least from its anti-aggregant effect on platelets, differing from aspirin.

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Enzymes involved in reduction of methyl p-nitrobenzoate in Escherichia coli B/r were oxygen-insensitive and precipitated between 30 and 60% ammonium sulfate saturation from cell-free extracts of the strain. The reductases were resolved by DEAE-cellulose column chromatography into three enzymes, NADH-linked, NAD (P) H-linked and NADPH-linked ones. These enzymes were flavoprotein which could be inactivated by dialysis aginst 1 M potassium bromide and could be reactivated by FMN. The NADH-linked and NAD (P) H-linked reductases were sensitive to dicumarol and exhibited menadione reductase activities. Aromatic nitro compounds with electron-withdrawing p-substituents were easily reduced by the NAD (P) H-linked reductase.

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Cyclic adenosine 3' : 5'-monophosphate (cyclic AMP) levels in six lines of rat ascites hepatoma cells were determined after the treatment with isoproterenol. The maximum increase of cyclic AMP levels was induced by the treatment with 10^-7 M of isoproterenol in each cell line, though the difference was observed at the time to reach the maximum levels. Following the treatment with 10^-7 M of isoproterenol, cyclic AMP levels increased by 55 to 80% of control in AH-44, AH-130 and AH-7974 cells, by 25 to 45% in AH-41C and AH-109A cells, and slightly in AH-13 cells. The combined cytotoxic effect of isoproterenol and mitromycin C was studied using AH-13, AG-44 and AH-130 cells. The cytotoxicity of mitomycin C on AH-44 and AH-130 cells was potentiated by the pretreatment with 10^-7 M of isoproterenol that was not cytotoxic by itself, but such a potentiation was not observed in AH-13 cells. The cyclic AMP levels were examined in the cells after the combined treatment. Mitomycin C by itself hardly affected the levels in three cell lines. In AH-44 and AH-130 cells, however, the period of the high levels of cyclic AMP was longer in the combined treatment than in the treatment with isoproterenol alone. On the other hand, the cyclic AMP level in AH-13 cells was hardly affected by each agent or the combined treatment. These results suggest that the combination effect of isoproterenol and mitomycin C is closely related to the increase of cyclic AMP in the cells treated with isoproterenol.

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A competitive enzyme immunoassay for methamphetamine with alkaline phosphatase labeled methamphetamine, Sepharose-antibody and p-nitrophenylphosphate as substrate was developed. The anti-methamphetamine antisera produced in rabbits by immunization with N-(4-aminobutyl) methamphetamine-BSA conjugate were specific for methamphetamine and showed low cross-reactivities with p-OH methamphetamine and amphetamine (metabolites of methamphetamine). The range of methamphetamine measurable by the enzyme immunoassay was 1 to 300 ng/tube. According to the assay, methamphetamine could be detected from urine and extract of hair.

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Pharmacological action of ionophore X537A was studied in taenia coli and aortic strips isolated from rabbit. These isolated smooth muscle preparations contracted by X537A (10^-5-10^-4 M). A removal of Ca ions from the buffer solution considerably reduced the contraction of taenia coli but not that of aorta. D 600 (methoxyverapamil, 10^-6 M) was without any effect in the contraction of both tissues by X537A (10^-4 M). However, papaverine (10^-4 M) and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride, 10^-4 M) inhibited X537A (10^-4 M)-induced contraction markedly in taenia coli but slightly in aorta. Inhibitory effects of these drugs were reversed in taenia coli by increasing Ca ion concentration in buffer solution but not in aorta. X537A (10^-4 M)-induced contraction of aorta was not affected by a pretreatment of rabbit with reserpine and preincubation of the isolated preparations with guanethidine (10^-6 M) or prazosin (10^-7 M). These results suggest that ionophore X537A might produce the contraction through an increase of Ca influx in isolated rabbit taenia coli which are little or not affected by D 600, whereas the contraction of rabbit aorta induced by X537A is mainly due to facilitation of release of Ca sequestered intracellularly.

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The extent and rate of absorption of phenytoin (PHT) from tablet and powder were studied in four healthy adult volunteers. It was demonstrated by urinary fecal excretion that the almost all quantity of PHT in tablet was absorbed through the gastrointestinal tract, and the observed values of the estimated free concentration (C_est.f) estimated from mixed saliva concentration of PHT in the multiple does were in fair agreement with the calculated values of that by using computer simulation in case of tablet. On the contary, the variations were observed in C_est.f using therapeutic does of PHT powder. The values of C_est.f at steady-state in tablet administration were higher than those in powder administration. The absorption ratio of PHT powder was low and variable, and decreased upon increase of does. The ratio calculated from the C_est.f values of both dosage form at steady-state were in good correspondence to the observed values of PHT excreted in feces.

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Carteolol, 5-(3-tert-butylamino-2-hydroxy) propoxy-3, 4-dihydrocarbostyril hydrochloride was found to be a beta-adrenergic partical agonist in the taenia caecum of guinea pig. Concentration response curves of carteolol and isoprenaline were parallelly shifted by propranolol (10^-7 M) suggesting that site of action of both the drugs was the same beta-adrenoceptor. The pD₂-values of carteolol obtained from the concentration action curves in mechanical response and increase of tissue concentration of cyclic AMP were significantly different from its pA₂-value against isoprenaline and its pK_i-value (negative log of its apparent dissociation constant). A possible explanation of our observation would seem to be as follows. Carteolol and isopranaline interact with the same beta-adrenoceptor where there may be two different sites : a binding site for agonist and binding site for antagonist.

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