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F J Hock

Publications and source records attributed to F J Hock.

12 recordsLinked to original sources
PubMed1993

Mnemogenic effects of injecting RA-octil, a CE-inhibitor derivate, systemically or into the basal forebrain.

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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies.

1. Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]bradykinin) is a new bradykinin (BK)-antagonist. It was tested in several in vitro assays and compared with D-Arg-[Hyp2,Thi5,8,D-Phe7]BK. 2. In receptor binding studies in guinea-pig ileum preparations, Hoe 140 showed an IC50 of 1.07 x 10(-9) mol l-1 and a KI value of 7.98 x 10(-10) mol l-1. 3. In isolated organ preparations Hoe 140 and D-Arg-[Hyp2,Thi5,8, D-Phe7]BK inhibited bradykinin-induced contractions concentration dependently, with IC50-values in the guinea-pig ileum preparation of 1.1 x 10(-8) mol l-1 and 3 x 10(-5) mol l-1, respectively. pA2 values in this tissue were 8.42 and 6.18, respectively. In the rat uterus preparation the IC50 value was 4.9 x 10(-9) mol l-1 for Hoe 140. D-Arg-[Hyp2, Thi5,8, D-Phe7]BK showed an IC50 of 4.0 x 10(-6) mol l-1. The IC50 values in the guinea-pig isolated pulmonary artery were 5.4 x 10(-9) mol l-1 and 6.4 x 10(-6) mol l-1, respectively. In the rabbit aorta no inhibitory effects on Des-Arg9-BK induced contractions were observed. 4. In cultured bovine endothelial cells, Hoe 140 antagonized (IC50 = 10(-8) mol l-1) bradykinin-induced endothelium-derived relaxing factor (EDRF) release and the bradykinin-induced increase in cytosolic free calcium (IC50 = 10(-9) mol l-1). 5. Hoe 140 (10 -7mol I1) totally suppressed the bradykinin-induced (10 8 to 10- mol I') prostacyclin (PGI2) release from cultured endothelial cells of bovine aorta. D-Arg-[Hyp2, Thi5'8, D-Phe7]BK (10- 7 mol I1- ) showed a weaker antagonism. 6. Taken together these results show that Hoe 140 is a highly potent bradykinin antagonist. It was two to three orders of magnitude more potent than D-Arg-[Hyp2, Thi5 8, D-Phe7]BK.

Animals↗
PubMed1991

Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies.

1. The potency, duration of action and tolerability of Hoe 140, a novel and highly potent bradykinin (BK) antagonist in vitro, has been tested in different in vivo models and compared with the well-known BK antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]BK. 2. Hoe 140 is highly potent and long acting in inhibiting BK-induced hypotensive responses in the rat. Four hours after s.c. administration of 20 nmol kg-1, inhibition still amounted to 60% whereas the effect of 200 nmol kg-1 of D-Arg-[Hyp2, Thi5,8, D-Phe7]BK was not significant. 3. BK-induced bronchoconstriction in guinea-pigs was strongly inhibited by Hoe 140. The magnitude and duration of inhibition confirmed the findings obtained in the blood pressure experiments in the rat. 4. Carrageenin-induced inflammatory oedema of the rat paw was considerably inhibited at i.v. doses between 0.1 and 1 mg kg-1. 5. In conscious dogs, intravenous doses of 0.01 and 0.1 mg kg-1 of Hoe 140 and D-Arg-[Hyp2, Thi5,8, D-Phe7]BK were well tolerated. At doses of 1 mg kg-1 adverse effects occurred that were attributed to the residual BK agonistic activity of both compounds. 6. Hoe 140 has been shown to be a highly potent and long acting BK antagonist in vivo in different animal species and models. This makes it appropriate to investigate further the physiological and pathophysiological role of BK.

Animals↗
PubMed1990

Interaction between catecholaminergic and opioid systems in an active avoidance task.

Male NMRI mice were given intravenous injections of the noradrenergic neurotoxin DSP4 or the vehicle 24 to 72 h prior behavioral testing. Animals were given 2 days of training on a one-way active avoidance task. Naloxone was given in one of three doses prior to training on Day 1 and Day 2 or prior to training on Day 1 only (saline was given prior to training on Day 2). There was a dose-dependent impairment of acquisition by naloxone in the vehicle-pretreated groups; 10 mg/kg naloxone produced a significant impairment of acquisition. Naloxone also modulated retention (Day 2) performance of the active avoidance task. For vehicle-pretreated mice, 1 mg/kg naloxone facilitated and 10 mg/kg naloxone-impaired performance on Day 2. DSP4 alone produced an impairment of acquisition of this task but had no effect on retention; Day 2 scores were slightly higher in the DSP4-pretreated group than in the vehicle-pretreated group. Naloxone produced somewhat different effects in DSP4-pretreated animals than in vehicle-pretreated animals. Naloxone (1 mg/kg) ameliorated the DSP4-induced impairment of acquisition; 10 mg/kg naloxone did not significantly alter the acquisition performance of this group. For the DSP4-pretreated mice that received naloxone before training on both days, the dose-response characteristics for retention scores were similar to those of vehicle-pretreated mice; 1 mg/kg naloxone was the facilitatory dose. However, for DSP4-treated mice that received naloxone before training on Day 1 only, there was a shift to the right in the effective facilitatory dose of naloxone. For these animals, 10 mg/kg naloxone but not 1 mg/kg naloxone significantly enhanced retention performance. We discuss these results in the context of a possible state-dependent modulation by naloxone in the DSP4-treated animals.

Animals↗
PubMed1989

Effects of the novel compound, Hoe 065, upon impaired learning and memory in rodents.

The effects of Hoe 065 (n-octyl 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo [3.3.0]octane-3-carboxylate maleate salt) were studied on the performance of mice and rats in different learning tasks. Hoe 065 prevented the disruption of memory induced by scopolamine administered before training. The results indicate that Hoe 065 improves cognitive function in different tasks.

Animals↗
PubMed1987

Drug influences on learning and memory in aged animals and humans.

In this article the effects of neurotransmitter systems or specific drugs on cognitive functions of aged animals and humans are reviewed. While there have been used many different pharmacologic and behavioral approaches to treat and test cognitive deficits in aged animals and geriatric or demented patients, there is still the question of the validity of animal models of human disorders. Attempts are made to show that there are parallels and similarities. These similarities suggest that the neurological and neurochemical changes observed may play common roles in similar behavioral deficits observed in aged animals and humans.

Aging↗
PubMed1986

Functional activity in the brain of socially deprivated rats produced by an active avoidance test after razobazam (Hoe 175) treatment: a 2-deoxyglucose study.

The 2-deoxyglucose (2-DG) autoradiographic method was used to map metabolic activity in the brain of socially deprivated rats during an active avoidance test. The method investigated the effects of razobazam during this learning test. The animals were socially deprivated for 5 weeks. On the first experimental day the animals were trained to avoid a footshock by jumping onto a platform. During training and testing, the total number of avoidance responses was scored. On the second day during one 2-DG session of 40 min, razobazam increased the avoidance score by 18% as compared to controls. Autoradiographs were analyzed using a two-dimensional densitometric method. The analysis of the brain structures showed a 22% reduction of optical density in the nucleus habenularis lateralis, a 25% increase in the caudal part of the nucleus accumbens, and a 13% increase in the frontal cortex in rats treated with razobazam, but no change in the amygdala. These results provide a preliminary concept to explain how the new compound razobazam produced a better learning performance in socially deprivated rats.

Animals↗
PubMed1985

Enhancing effects of Hoe 175 on memory in mice.

These experiments investigated the effects of the nootropic compound Hoe 175 [3,8-dimethyl-4-phenyl-5,6,7,8-tetrahydro-pyrazolo-(3,4-b) (1,5)-diazepine-1H,4H-5,7-dione] on retention performance of mice in three training tasks. When administered prior to both training and retention testing on a one-trial inhibitory avoidance task, Hoe 175 (6-25 mg/kg PO) attenuated the amnestic effect of transcorneal electroconvulsive shock. Post-training administration of Hoe 175 enhanced retention of otherwise untreated mice in both inhibitory (3-12 mg/kg IP) and active avoidance (1-25 mg/kg IP) learning tasks. The drug was most effective at intermediate doses. The enhancing effect of post-training administration of Hoe 175 was time-dependent: enhancement of retention was obtained with injections administered 2 h but not 6 h after training. The findings are interpreted as suggesting that Hoe 175 affects retention performance through influences on memory storage and retrieval.

Amnesia↗
PubMed1983

Cholinergic system in the toad's (Bufo bufo L.) visual system.

The brain structures mediating the prey-catching behavior of the toad have been described in earlier studies but none of these studies has identified the transmitter systems in the optic tectum responsible for this behavior. Behavioral tests with different test compounds provide evidence that the cells responsible for the orienting, jumping, and snapping behaviors associated with feeding in toads are normally inhibited by cholinergic synapses.

Acetylcholine↗
PubMedDate not supplied

Neurochemical effects of the synthetic ACTH4-9-analog Hoe 427 (Ebiratide) in rat brain.

The ACTH4-9-analog Hoe 427 systemically injected in a dose range from 0.01-10 micrograms/kg caused a fall in acetylcholine (ACh) content in different brain areas of the rat. This effect occurred 0.5 hour after a single administration and lasted up to 24 hours. The decrease in ACh content induced by Hoe 427 was more pronounced when the animals were pretreated with dexamethasone (over 7 days 1 mg/kg SC, daily). Coadministration of the choline uptake inhibitor hemicholinium-3 (HC-3) and Hoe 427 potentiated the decrease in ACh content induced by HC-3. In the same dose range Hoe 427 acutely evoked an increase of the activity of the enzyme choline acetyltransferase as well as an elevation of brain cyclic GMP content. These data indicate that Hoe 427 enhances ACh metabolism in rat brain after systemic administration.

Acetylcholine↗
PubMedDate not supplied

Learning and memory processes of an ACTH4-9 analog (ebiratide; Hoe 427) in mice and rats.

These experiments investigated the effects of the new ACTH4-9 analog ebiratide (Hoe 427) [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH-(CH2)8-NH2 X 3 CH3COOH] on memory processes in mice and rats in five training tasks. With all five training and testing procedures (inhibitory avoidance test with ECS- or scopolamine-induced amnesia, up-hill avoidance, one-way shuttle box avoidance and eight-arm radial maze) ebiratide was most effective in a dose range of 1-10 micrograms/kg SC.

Adrenocorticotropic Hormone↗