摘要:

AbstractEvidence is reviewed to assign the role of cholecystokinins in the cognitive and memory processes. Rat brain contains about 550 ng of CCK‐8. When injected, icv or sc, in doses of less than 100 ng of CCK or caerulein, these peptides prevent experimental amnesia and prolong extinction of the already‐learned tasks. Caerulein is nearly 10 times as potent as CCK‐8, and the effects of both peptides are long‐lasting. Pretreatment with these peptides also prevents scopolamine‐induced amnesia, and reverses the ACh depletion in the frontal and temporal cortices as well as in the hippocampus. CCK‐8 antagonists in small doses produce complete amnesia, further supporting the hypothesis that endogenous CCK‐8 modulates the memory processes in the brain. Neurochemical data suggest participation of the NMDA receptors, protein kinase C, and protein synthesis in the action of CCK‐8 and caerulein. Sub‐diaphragmatical vagotomy abolishes the memory‐enhancing effects of these peptides when administered peripherally. Thus, CCK‐8 and caerulein are likely to affect not only the receptors localized in the CNS, but also to stimulate peripheral receptors associated with the vagus. Alternatively, the vagus may be the major pathway for CCK transport from the viscera

ISSN:0272-4391    

DOI:10.1002/ddr.430210402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractRWJ 20085 is a potent, long‐acting local anesthetic that has been studied in vivo and in vitro relative to several clinically active agents. In mice, RWJ 20085 [ED50= 0.0078% (0.0053–0.011%)] was more potent by perineural infiltration than bupivacaine [ED50= 0.035% (0.026–0.046%)], etidocaine [ED50= 0.025% (0.016–0.035%)], or lidocaine [ED50= 0.18% (0.13–0.26%)]. The onset of action of each compound was 5 minutes, and the duration was 90 minutes for RWJ 20085 and 30 minutes for bupivacaine or etidocaine while lidocaine was active for only 15 minutes. In the rabbit corneal assay, RWJ 20085 [ED50= 0.012% (0.0049–0.023%)] was more potent than bupivacaine [ED50= 1.4% (0.47–3.05%)]. The lowest topical local anesthetic ED50of each agent was observed within 5 or 15 minutes after administration, and RWJ 20085 was active for 300 minutes, whereas bupivacaine and etidocaine were active for 90 or 45 minutes, respectively. In the guinea pig intradermal assay RWJ 20085 [ED50 = 0.017% (0.0094–0.028%)], bupivacaine [ED50= 0.016% (0.0078–0.028%)], and etidocaine [ED50= 0.02% (0.0093–0.042%)] were equipotent while lidocaine [ED50= 0.072% (0.040–0.12%)] was less potent. The onset of action of each compound was 5 minutes. The duration of action of RWJ 20085 and etidocaine was 60 minutes, whereas bupivacaine and lidocaine were active for 45 and 15 minutes, respectively. In the frog isolated‐sciatic nerve preparation, similar concentrations of RWJ 20085 (2.5 × 10−3M) and lidocaine (5.0 × 10−3M) produced a 50% reduction of the amplitude of the pretreatment action potential; however, bupivacaine and etidocaine were each effective at a lower concentration (5.0 × 10−4M). When their intramuscular therapeutic ratios (TR = lethal dose LD50/local anesthetic ED50) were calculated in mice, the therapeutic ratio of RWJ 20085 (82) was less than that of etidocaine (103) but was larger than that of either lidocaine (36) or bupivacaine (29). Calculation of the therapeutic ratios by using the intravenous LD50values suggests that lidocaine would have the smallest margin of safety if inadvertently administered by the intravenous route. The therapeutic ratios of the other agents were larger than that of lidocaine; however, there was little difference among them. RWJ 20085 has a low potential for dermal irritation as shown in rabbits and has no liability for contact sensitization as shown in guinea pigs. RWJ 20085 may have clinical utility as an injectable

ISSN:0272-4391    

DOI:10.1002/ddr.430210403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe absorption of magnesium (Mg2+) was measured after oral administration to dogs as a sustained‐release MgCl2·6H2O OROS formulation (MgCl2) or as magnesium aspartate hydrochloride (MAH). The compounds and their respective placebos were given at five 90 min intervals in 7.5 mEq doses (sequential protocol) or in ascending daily doses of 7.5, 22.5, and 45 mEq over 3 days (ascending protocol). Urinary excretion of Mg2+over 24 hr was significantly increased compared to placebo in the dogs given sequential MgCl2or MAH and was two‐fold greater in the MgCl2‐treated group compared to the MAH group. Plasma Mg2+increased more rapidly in the MgCl2‐treated dogs but was identical in both groups 1 hr after the fifth sequential dose. Ascending daily doses of MgCl2and MAH increased urinary Mg2+and plasma Mg2+maximally 2–4 hr after each dose; the magnitude of the effect was dose‐dependent in the MgCl2group. Sequential doses of MgCl2or MAH increased urinary Ca2++excretion by 1.06 and 1 mEq/24 hr respectively while the ascending doses of 22.5 and 45 mEq MgCl2produced significantly greater urinary Ca2+excretion than the same doses of MAH. Plasma Ca2+was not changed by either Mg2+salt in either dose regimen. The data indicate that Mg2+is readily absorbed after oral administration in the form of either MgCl2or MAH, but MgCl2is absorbed more rapidly. Increased urinary excretion of Ca2+after MgCl2or MAH may reflect a displacement of tissue

ISSN:0272-4391    

DOI:10.1002/ddr.430210404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractCK‐2130 is a new imidazolone developed to treat congestive heart failure. We compared CK‐2130 to four inodilators and ouabain in several pharmacologic models. Intravenous (i.v.) administration of CK‐2130 to pentobarbital‐anesthetized dogs (0.03 to 1 mg/kg) relatively selectively increased myocardial dP/dT when compared to the dual positive inotropic and vasodilator activity of milrinone, enoximone, imazodan, and piroximone. Milrinone and piroximone (600 mg/kg, p.o., and 30‐300 mg/kg, i.p.) were central nervous system depressants in mice. CK‐2130 (100 mg/kg, i.v. and 600 mg/kg, i.p. and p.o.) was not depressant. Gastric acid secretion in the guinea pig was not affected by CK‐2130 (1 mg/kg, i.v.) and was inhibited by milrinone (1 mg/kg, i.v.) and enhanced by enoximone (1 mg/kg, i.v.). CK‐2130 and milrinone (0.03‐1 mg/kg, i.v.) did not affect rabbit sciatic nerve‐gastrocnemius muscle function. CK‐2130, piroximone, imazodan, and milrinone (100 μM) did not affect sympathetic neurotransmission, postsynaptic receptors, or guinea‐pig nonvascular smooth muscles but relaxed canine arteries and veins. Ouabain (1‐100 μM) initially facilitated, then inhibited, sympathetic neurotransmission, contracted vascular and non‐vascular smooth muscles, enhanced the vas deferens contraction to norepinephrine, and inhibited uterine contractions to bradykinin (10 μM). CK‐2130, milrinone, piroximone, and imazodan (0.1 to 100 μM) inhibited human platelet aggregation produced by adenosine diphosphate and sodium arachidonate. Thus, CK‐2130, a relatively selective positive inotrope, should be devoid of adverse central nervous system; neural, smooth, and skeletal muscle; and gastrointestinal side effects associated w

ISSN:0272-4391    

DOI:10.1002/ddr.430210405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractA multicenter study to compare the antidepressant efficacy and the tolerance of moclobemide (Ro 11‐1163) to clomipramine was performed in parallel groups of patients with minor depression. The duration of the study was 6 weeks, with weekly assessments by means of Hamilton Scale of Depression (HRDS) and the Clinical Global Impression (CGI). The efficacy of moclobemide was found to be as good as that of clomipramine. The results for tolerability were possibly in favor of moclobemide. It was recommended that consumption of tyramine‐containing foods be kept to a minimum or avoided and no hypertensive crises were repor

ISSN:0272-4391    

DOI:10.1002/ddr.430210406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430210401

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY