Drugs online research references
Psychopharmacology (Berl). 1993;111(4):442-8.
Mnemogenic effects of injecting RA-octil, a CE-inhibitor derivate, systemically or into the basal forebrain.
Gerhardt P, Hasenohrl RU, Hock FJ, Huston JP.
Institute of Physiological Psychology I, University of Dusseldorf, Germany.
The aim of this study was to investigate the effects of systemically or intracerebrally administered RA-octil, a derivative of the angiotensin converting enzyme (CE)-inhibitor ramipril, on memory and reinforcement and to compare its effectiveness with that of the neurokinin substance P (SP). In the first experiment systemic post-trial application of RA-octil and SP in the rat enhanced habituation, a learning task which does not require motivational treatments. Unlike SP, injection of RA-octil did not have reinforcing effects as measured with a conditioned place preference task. In the second experiment, a facilitation of inhibitory avoidance learning was obtained by injection of RA-octil or SP unilaterally into the basal forebrain immediately after the learning trial. In contrast, a 5 h delayed injection of RA-octil had no effects on learning. The results demonstrate memory-enhancing effects of RA-octil after systemic application as well as after injection into the basal forebrain. Furthermore, the mnemogenic effects of SP after central and peripheral administration were confirmed. Since RA-octil, although being structurally closely related to CE-inhibitors, does not affect plasma CE, yet exhibits mnemogenic effects, it is possible that "cognition-enhancing" actions of CE-inhibitors are dissociable from their action within the renin-angiotensin system.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7532864&dopt=Abstract
Circ Res. 1994 Mar;74(3):441-7.
Importance of sympathetic innervation in the positive inotropic effects of bradykinin and ramiprilat.
Minshall RD, Yelamanchi VP, Djokovic A, Miletich DJ, Erdos EG, Rabito SF, Vogel SM.
Department of Anesthesiology, University of Illinois College of Medicine, Chicago 60612.
Isolated rat left atria or right ventricular strips were electrically stimulated at a constant frequency. The amplitude of twitch contractions, thus elicited, rose as a function of stimulation intensity because of increases in the evoked release of sympathetic catecholamines. Bradykinin had no effect on contractile force in preparations paced at a minimal intensity (threshold). By contrast, bradykinin (1 nmol/L to 1 mumol/L) markedly increased twitch contractile force when the preparations were paced at a high intensity (two to three times threshold). The EC50 for the positive inotropic action of bradykinin averaged 42 nmol/L. Ramiprilat (1 mumol/L), an angiotensin I-converting enzyme/kinase II inhibitor, shifted the EC50 for bradykinin to approximately 2 nmol/L. Ramiprilat (1 mumol/L) per se also produced a modest positive inotropic effect. The effects of bradykinin and/or ramiprilate were inhibited by HOE 140 (300 nmol/L), a bradykinin B2-receptor antagonist. Propranolol (1 mumol/L), a beta-adrenoceptor blocker, abolished the effects of bradykinin. After the destruction of sympathetic nerve endings by use of 6-hydroxydopamine, bradykinin no longer exerted a positive inotropic action. Cocaine (10 micrograms/mL), an inhibitor of catecholamine reuptake, potentiated the effect of bradykinin. Bradykinin did not affect the positive inotropic response to tyramine (10 mumol/L), whereas cocaine blocked it. Furthermore, bradykinin did not modify the dose-response curves for added norepinephrine. omega-Conotoxin (100 nmol/L) inhibited the positive inotropic effect of intensified stimulation and bradykinin potentiation. Bradykinin is suggested to facilitate the evoked release of sympathetic catecholamines and thereby cause a positive inotropic effect.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8118952&dopt=Abstract
J Cardiovasc Pharmacol. 1987;9 Suppl 2:S31-6.
Captopril-induced increase in coronary flow: an SH-dependent effect on arachidonic acid metabolism?
van Gilst WH, van Wijngaarden J, Scholtens E, de Graeff PA, de Langen CD, Wesseling H.
The effect of captopril (80 micrograms/ml) on coronary flow in the isolated rat heart was compared with the effects of a non-sulfhydryl-converting enzyme inhibitor, ramipril (15 micrograms/ml), and of a sulfhydryl-containing compound with no converting enzyme-inhibiting properties, glutathione (112 micrograms/ml). Drug concentrations were equipotent in their effect on angiotensin I pressor response and equimolar with respect to the sulfhydryl group. Cyclooxygenase products or their stable metabolites (TXB2, 6-keto-PGF1 alpha and PGE2) were measured in the coronary effluent. Furthermore, the effect of mepacrin (1 microM), indomethacin (1 microM), and FPL 55712 (10 microM) on the changes in coronary flow induced by captopril was studied. Both captopril- and glutathione-treated hearts showed a significant increase in coronary flow already after 5 min treatment. After 60 min treatment, coronary flow was further increased to 185 +/- 9% for captopril-treated hearts and to 210 +/- 11% for glutathione-treated hearts when compared to saline treatment. Ramipril treatment resulted in a slower increase in coronary flow, which was significant after 20 min treatment. After 60 min treatment, this increase was 122 +/- 3% when compared to saline-treated hearts. This effect of ramipril was associated with a significant increase in 6-keto-PGF1 alpha overflow when compared to saline-treated hearts. Captopril and glutathione had no significant effect on overflow of the measured cyclooxygenase products. The effect of captopril and glutathione on coronary flow appeared to be dose dependent in an equimolar range. Simultaneous mepacrin treatment diminished the effect of captopril on coronary flow; indomethacin had no effect, and FPL 55712 potentiated the effect of captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2441198&dopt=Abstract
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