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H I Jacoby

Publications and source records attributed to H I Jacoby.

31 records · Page 2Linked to original sources
PubMed1985

Mu and delta, but not kappa, opioid agonists induce contractions of the canine small intestine in vivo.

Extraluminal strain gage transducers were sutured along the transverse axis of the duodenum in order to monitor circular muscle contractile activity in the pentobarbital anesthetized dog. Administration by intravenous bolus of a variety of mu- and delta-directed opioid ligands resulted in a dose-dependent increase in duodenal contractile activity. In contrast, all kappa-directed ligands were devoid of stimulatory activity. Naloxone reversed the effects of normorphine and [Met5]enkephalin but was 20 times more effective against normorphine than [Met5]enkephalin. Based on the inactivity of all kappa ligands examined and the differential potency of naloxone against [Met5]enkephalin and normorphine, we suggest that this model may be useful in the classification of opioid ligands as to their receptor selectivity in vivo. Further, these data indicate that the stimulation of duodenal contractile activity is not mediated by enteric kappa receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1984

Tachykinin-like central activity of neuromedin K in mice.

Neuromedin K, a decapeptide isolated from porcine spinal cord and suggested to have tachykinin-like activity in vitro, produced reciprocal hind-limb scratching when injected intrathecally to mice. Neuromedin K was 20-60 times less potent in producing scratching (on a molar basis) than substance P, kassinin, eledoisin or physalaemin. The activity of neuromedin K was blocked by the substance P antagonist [D-Pro2D-Trp7.9]substance P at doses of antagonist which effectively blocked the activity of the other tachykinins. These data provide the first evidence for tachykinin-like activity of neuromedin K in the central nervous system.

Animals↗
PubMed1984

Antisecretory activity of fenoctimine in rat and dog.

Fenoctimine (4-(diphenylmethyl)-1-[(octylimino)methyl]piperidine) sulfate was evaluated for gastric antisecretory activity in the acute gastric fistula rat and chronic gastric fistula dog. It showed potent gastric antisecretory activity of long duration in the rat, and was more potent on a mg/kg basis than cimetidine. In the dog, fenoctimine showed significant activity against gastrin tetrapeptide, histamine, and bethanechol. It was least potent against bethanechol, indicating a lack of significant anticholinergic activity in the dog at the doses tested. It had a long duration of action in the dog with doses of 6 mg/kg, showing significant activity even at 24 hr. Fenoctimine does not appear to fit the spectrum of activity associated with other known antisecretory agents and may have a unique mechanism of action related to effects directly on parietal cells.

Administration, Oral↗
PubMed1983

4-(Diphenylmethyl)-1-[(imino)methyl]piperidines as gastric antisecretory agents.

4-(Diphenylmethyl)-1-piperidinemethanimine (1) is a potent oral gastric antisecretory agent in rats but contains a strong anticholinergic component. Since a nonanticholinergic gastric antisecretory drug would be useful in the treatment of peptic ulcer disease, a program was initiated by us to find such an agent based on 1. Compound 1 contains structural elements common to the anticholinergics atropine and homatropine. Studies on the structure-activity relationships of these compounds and their derivatives have revealed certain modifications that diminish or abolish anticholinergic activity. The application of these modifications to the design of analogues of 1 afforded an antisecretory compound, 4-(diphenylmethyl)-1-[(octylimino)methyl]piperidine (3h, fenoctimine), which exhibited no anticholinergic activity. Fenoctimine is undergoing clinical trial as a gastric antisecretory drug.

Animals↗
PubMed1980

Cardiovascular profile of mixidine fumarate, a compound which attenuates myocardial chronotropic responses.

The effect of mixidine fumarate on myocardial chronotropic responses to various stimulants was examined. Mixidine decreased elevated heart rate in the anesthetized dog to basal levels. It produced a dose-related decrease in heart rate elevated reflexly by aminophylline, by beta adrenergic stimulation induced by isoproterenol, by sympathetic nerve stimulation and by intravenous infusion of glucagon. Mixidine attenuated the increase in contractile force produced by sympathetic nerve stimulation but not that induced by isoproterenol. The compound antagonized the increase in rate of isolated guinea-pig atria induced by both isoproterenol and histamine. In the conscious dog, mixidine caused no decrease in resting heart rate, mean arterial pressure and cardiac output. It reduced atropine-induced sinus tachycardia as well as that induced by treadmill exercise. Experiments in the dog heart-lung preparation indicated that attenuation of an epinephrine-induced sinus tachycardia led to a decrease in myocardial oxygen consumption and an increase in myocardial efficiency. These studies suggest that mixidine fumarate induces an antichronotropic activity by a direct effect on the sinoatrial node and by attenuating sympathetic nervous system input to the heart.

Aminophylline↗
PubMed1979

2-Mercaptoacetamidines as gastric antisecretory agents.

A series of N-substituted 2-mercaptoacetamidines was synthesized and evaluated for gastric antisecretory activity in dogs stimulated with gastrin tetrapeptide. The most potent analogues showed 80--95% inhibition of acid secretion after an oral dose of 8 mg/kg. Thus, these compounds represent a new structural type having significant antisecretory activity. Disulfides had essentially the same antisecretory potency as the corresponding mercaptoacetamidines, indicating a metabolic interconversion. Alkylation of the mercapto group decreased potency. Higher carboxamidine homologues such as 2- and 3-mercaptopropionamidines had very low activity. Hydroxyacetamidines and mercaptoacetamides also had low potency. Side effects observed with this series of compounds included emesis, tachycardia, and gastric bleeding.

Amidines↗
PubMed1979

Antisecretory actions of aminophylline in the rat and dog.

The effect of aminophylline on gastric acid secretion has been studied in the rat and dog. Aminophylline was shown to possess antisecretory activity when given either by oral or parenteral administration in an acute gastric fistula rat preparation. In the chronic gastric fistula dog aminophylline at 50 mg/kg intragastrically induced a small but significant stimulation of basal acid secretion. This dose of aminophylline also significantly inhibited acid secretion induced by gastrin tetrapeptide, and 2-deoxy-D-glucose but did not block acid secretion induced by histamine.

Aminophylline↗
PubMed1978

Possible ion-pair-mediated absorption of mixidine I: partitioning and lethality studies.

Mixidine, a very soluble base which is completely ionized in all physiological fluids, was found to form ion-pairs as demonstrated by its ability to partition into 1-butanol from acidic solutions. A similar relationship was observed for the effect of acids on the absorption of intraduodenally and orally administered solutions of mixidine in rats (as determined by lethality). Studies also demonstrated that the pH-lethality effects were not specific for a particular counterion. Mixidine was more lethal when administered intraduodenally than when administered orally, and the counterions per se were not lethal in the doses used.

Absorption↗
PubMedDate not supplied

A-18-famide and F-8-famide, endogenous mammalian equivalents of the molluscan neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2), inhibit colonic bead expulsion time in mice.

Morphine and the two endogenous mammalian FMRFamide (Phe-Met-Arg-Phe-NH2)-related peptides known as morphine-modulating neuropeptides, F-8-Famide (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) and A-18-Famide (Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe -NH2), were administered intracerebroventricularly (ICV) to mice and the effect of each on colonic bead expulsion time was measured. Each of the three compounds delayed expulsion of a 3 mm glass bead placed in the distal colon. A-18-Famide was more potent than F-8-Famide [ED 50 = 2.3 micrograms (1.2 nmole) and 13.9 micrograms (13.0 nmole), respectively]. A-18-Famide: 1) did not block morphine-induced delay of bead expulsion time, and 2) was blocked by simultaneous administration (ICV) of 1.0 microgram of the competitive opiate antagonist naloxone. These data demonstrate apparent opioid modulatory or agonist-like, rather than antagonist-like, properties of A-18-Famide and F-8-Famide.

Animals↗
PubMedDate not supplied

FMRFamide enhances acetylcholine-induced contractions of guinea pig ileum.

Isolated guinea pig ilea were contracted with acetylcholine (ACh) in the absence and presence of the neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2). FMRFamide (0.17-17 microM) enhanced ACh-induced contractions (observed as a leftward shift of the dose-response curve and increase in Emax) with maximal effect at 1.7 microM. FMRFamide had no effect when administered alone. These results extend the demonstration of a FMRFamide/ACh interaction to mammalian tissue and support the concept that FMRFamide, or mammalian equivalents, could play a modulatory role in mammals.

Acetylcholine↗