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Biomedical subjects

J C Hendrix

Publications and source records attributed to J C Hendrix.

11 recordsLinked to original sources
PubMed1995

Novel alkoxy-oxazolyl-tetrahydropyridine muscarinic cholinergic receptor antagonists.

The purpose of the present studies was to compare a novel series of alkoxy-oxazolyl-tetrahydropyridines (A-OXTPs) as muscarinic receptor antagonists. The affinity of these compounds for muscarinic receptors was determined by inhibition of [3H]pirenzepine to M1 receptors in hippocampus, [3H]QNB to M2 receptors in brainstem, and [3H]oxotremorine-M to high affinity muscarinic agonist binding sites in cortex. All of the compounds had higher affinity for [3H]pirenzepine than for [3H]QNB or [3H]oxotremorine-M labeled receptors, consistent with an interpretation that they are relatively selective M1 receptor antagonists, although none were as selective as pirenzepine. In addition, dose-response curves were determined for antagonism of oxotremorine-induced salivation (mediated by M3 receptors) and tremor (mediated by non-M1 receptors) in mice. In general, the A-OXTPs were equipotent and equieffective in antagonizing both salivation and tremor, although there were modest differences for some compounds. Dose-response curves also were determined on behavior maintained under a spatial-alternation schedule of food presentation in rats as a measure of effects on working memory. The A-OXTPs produced dose-related decreases in percent correct responding at doses three- to ten-fold lower than those which decreased rates of responding. However, only one compound, MB-OXTP, produced effects on percent correct responding consistent with a selective effect on memory as opposed to non-memory variables. The present results provide evidence that these alkoxy-oxazolyl-tetrahydropyridines are a novel series of modestly M1-selective muscarinic receptor antagonists, and that one member of the series, MB-OXTP, appears to be more selective in its effects on memory than previously studies muscarinic antagonists.

Animals↗
PubMed1993

Comparative behavioral and neurochemical activities of cholinergic antagonists in rats.

The comparative behavioral and neurochemical activities of the muscarinic cholinergic antagonists scopolamine, trihexyphenidyl and pirenzepine, and the nicotinic cholinergic antagonist mecamylamine were evaluated in rats. The three muscarinic antagonists, but not the nicotinic antagonist, impaired memory performance in a spatial alternation task. The minimal effective doses required to disrupt behavior were 0.03, 1.0 and 10 mg/kg for scopolamine, trihexyphenidyl and pirenzepine, respectively. Scopolamine and trihexyphenidyl inhibited ex vivo binding of [3H] pirenzepine to M1 receptors in cerebral cortex, indicating ready penetration into the brain. In contrast, pirenzepine penetrated into the brain at relatively high doses, suggesting poor penetration into the brain. Scopolamine and trihexyphenidyl, but not pirenzepine, inhibited [3H]quinuclidinyl benzilate binding to brain stem M2 receptors ex vivo after subcutaneous administration. In addition, scopolamine and trihexyphenidyl, but not pirenzepine, decreased acetylcholine (ACh) levels in striatum and hippocampus, presumably by increasing ACh release by blocking ACh feedback inhibition at M2 receptors. Scopolamine and trihexyphenidyl also produced modest decreases in levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in striatum, most likely due to blockade of M1 heteroreceptors on dopamine nerve terminals. The present results are consistent with the interpretation that muscarinic antagonists impair memory performance in rats, at least in part, by blocking M1 muscarinic receptors. The present results do not support a role for blockade of M2 receptors. Further research is needed to determine the extent to which blockade of other (M3, M4, M5) muscarinic receptor subtypes contributes to the memory-impairing effects of muscarinic cholinergic antagonists.

Acetylcholine↗
PubMed1990

Interactions between scopolamine and muscarinic cholinergic agonists or cholinesterase inhibitors on spatial alternation performance in rats.

The effects on working memory of the muscarinic cholinergic agonists oxotremorine, arecoline, RS86 and pilocarpine, and the cholinesterase inhibitors physostigmine and tetrahydroaminoacadine were investigated in male F344 rats. Working memory was assessed by behavior maintained under a spatial alternation schedule of food presentation in which the interval between trials was varied from 2 to 32 sec. Under control conditions the percentage of correct responses decreased as the retention interval was varied from 2 to 32 sec. Administered alone the cholinergic agonists oxotremorine (0.01-0.1 mg/kg), arecoline (3-30 mg/kg), RS86 (0.3-3 mg/kg) and pilocarpine (0.3-3.0 mg/kg), and the cholinesterase inhibitors physostigmine (0.01-0.1 mg/kg) and tetrahydroaminoacridine (0.3-3.0 mg/kg) either had no effect on or produced dose-related deficits in working memory and decreases in response rates. The muscarinic antagonist scopolamine (0.1 mg/kg) produced retention interval-dependent decreases in the percentage of correct responding and rates of responding. The cholinergic agonists and tetrahydroaminoacridine failed to reverse the effects of scopolamine. However, physostigmine produced a dose-dependent reversal of the working-memory deficits and response-rate decreasing effects of scopolamine. The present results are consistent with the interpretation that drugs which primarily enhance M2 muscarinic cholinergic transmission are ineffective in enhancing working memory or in reversing scopolamine-induced deficits in working memory.

Animals↗
PubMed1988

Anthelmintic activity of continuous low doses of fenbendazole into the rumen of sheep.

Fenbendazole (FBZ) was continuously infused for 30 days into the rumen of 103 lambs which had mature or developing benzimidazole-susceptible or thiabendazole-resistant Haemonchus contortus and susceptible Trichostrongylus colubriformis infections. Ovicidal, larvicidal and adulticidal activities were exhibited against benzimidazole-susceptible and benzimidazole-resistant H. contortus worms by FBZ at a dose level of greater than or equal to 0.2 mg kg-1 body weight day-1. Reasonably consistent high level efficacy against H. contortus was obtained with dose levels greater than 0.4 mg kg-1. Excellent control of susceptible T. colubriformis worms was achieved with the lowest dose tested of 0.4 mg kg-1 day-1. The intraruminal infusion critical study method is a tool to determine the feasibility of incorporating a candidate anthelmintic compound in a continuous sustained-release rumen device formulation. The anthelmintic profile of FBZ obtained by low-level intraruminal administration suggests that it would be a potential candidate.

Animals↗
PubMed1987

Protection of lambs with a purified metabolite of exsheathed third-stage Haemonchus contortus larvae.

Helminth-free lambs (approx 4 months old) were inoculated SC with a purified metabolite of exsheathed third-stage Haemonchus contortus larvae. The metabolite was obtained from in vitro cultivation and was identified as XL3FA1. After 3 periodic XL3FA1 inoculations, lambs were challenge exposed with H contortus. Multiple vaccinations with XL3FA1 did not inhibit the development of worm populations in the lambs; however, worm egg production seemed to be inhibited.

Animals↗
PubMed1983

In vitro activity of various anthelmintic compounds against Haemonchus contortus larvae.

Twenty-five known anthelmintic compounds were evaluated in vitro against the highly motile exsheathed non-feeding third-stage of Haemonchus contortus larvae. Activity was based on lack of motility or death of larvae after 24 h of chemical exposure. Six compounds (avermectins, closantel, levamisole, morantel, phenylhydrazone and ticarbodine) were active at a concentration of 100 micrograms cm-3 or less. The most active compounds were avermectins and levamisole. When higher in vitro concentrations were used, ten compounds (bephenium, coumaphos, dichlorovos, disophenol, hygromycin b, methyridine, parbendazole, phenothiazine, pyrantel and thiabendazole) exhibited activity. Nine compounds were found to be inactive; among these were the new benzimidazoles, i.e., albendazole, fenbendazole, mebendazole and oxibendazole. Because of the inactivity of the new benzimidazoles, this in vitro system is unsuitable as a routine screening tool. Also, the system appears to favor drugs that act quickly through percuticular entry. In an initial group of 5280 untested compounds, 254 (4.8%) exhibited in vitro activity at 100 micrograms cm-3 against the non-feeding larvae stage. The exogenous and in vitro cultivation techniques required for collecting, cleaning and exsheathing the larvae are described.

Animals↗
PubMed1982

Diminutive polyps: histopathology, spatial distribution, and clinical significance.

This retrospective study of 329 diminutive colon polyps revealed that 49.2% of the polyps were neoplastic, whereas 49.9% were nonneoplastic. 36.8% of the polyps were metaplastic, and 0.9% had mixed metaplastic and adenomatous components. The metaplastic polyps had a predominance in the distal portion of the large bowel, with 76.9% being located distal from the splenic flexure and 52.9% being located in the rectosigmoid area. Neoplastic polyps were distributed throughout the colon, with 65.4% located from the splenic flexure distally and 34.5% located proximal to the splenic flexure. These findings suggest that a much larger proportion of diminutive polyps are neoplastic and therefore at risk to progress to carcinoma than previously considered.

Adult↗