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At least 1,351 records · Page 75Linked to original sources
PubMed1975

Long acting delivery systems for narcotic antagonists II: release rates of naltrexone from poly(lactic acid) composites.

Parallel in vitro and in vivo release rates of tritiated naltrexone from poly(lactic acid) composites were studied. The in vitro release of naltrexone was 67% of the dose over a 35-day test period, while the in vivo release was only 24% within 70 days. Apparently, an exchange of the tritium for the hydrogen of the body water takes place, indicating that urinary excretion radioactivity is not a reliable measure for estimating the naltrexone released. Naltrexone-poly(lactic acid) composites showed effective blocking action to morphine in rats (24 days), dogs (29 days), monkeys (20 days), and mice (21 days).

Animals↗
PubMed1978

Three-dimensional molecular illustrations II: Isoelectrostatic energy contour spheres of influence applied to narcotic molecules.

A computer-generated method using quantum mechanics was applied to the calculation and subsequent plotting of nonperspective three-dimensional illustrations of molecules in vacuo. The purpose was to generate isoelectrostatic energy contour spheres for larger molecules and current drugs. The molecules chosen, morphine, meperidine, and alphaprodine, possess similar pharmacological properties. Minor configurational manipulation of meperidine and alphaprodine molecules was made to approximate the spatial configuration of the rigid morphine molecule so that direct comparisons were possible. Common areas of reactivity, potential energy minima, net atomic charges, spatial regions, and near neighbor influences are considered.

Computers↗
PubMed1979

Cobaltous chloride-induced hypothermia. II: Pretreatment with sympathoplegics, antihistamines, and narcotic antagonists.

Body temperature depression was noted in rats, mice, and hamsters following intraperitoneal cobaltous chloride administration (25 mg/kg). Intracerebral cobalt injection elicited hypotermia in rats and mice but not in hamsters. Body temperature depression appeared to be centrally mediated in rats and mice and peripherally mediated in hamsters. The effect of intraperitoneal and intracerebral pretreatment with phentolamine, diphenhydramine, propranolol, cimetidine, and naloxone on the mouse rectal temperature response to cobalt (25 mg/kg ip) was noted. Systemic phentolamine injection (intraperitoneal) did not alter the cobalt response, whereas intracerebral administration partially antagonized cobalt-induced hypothermia, indicating that antagonism was mediated centrally. Pretreatment with propranolol and cimetidine failed to modify the temperature response. Intracerebral diphenhydramine did not influence cobalt hypothermia. However, this agent reduced the cobalt response when given intraperitoneally, presumably through a peripheral inhibitory mechanism. The intracerebral injection of naloxone 30 min prior to cobalt slightly enhanced hypothermia, apparently through a central action. Intracerebral 6-hydroxydopamine injection depleted brain norepinephrine and dopamine but exhibited no apparent influence on cobalt-induced hypothermia.

Animals↗
PubMed1998

Modeling acute and chronic toxicity of nonpolar narcotic chemicals and mixtures to Ceriodaphnia dubia.

The response of the daphnid Ceriodaphnia dubia to six widely used industrial chemicals acting through nonpolar narcosis and a mixture was determined. Toxicological effect levels were based on reasonably steady-state, measured concentrations. Reproductive IC50S were 149 microM benzene, 82 microM trichloroethylene, 35 microM toluene, 31 microM ethylbenzene, 26 microM m-xylene, and 4 microM tetrachloroethylene. A QSAR describing 2-day LC50S as a function of log Kow accounted for 90.97% of the variation in response across chemical. A similar QSAR for chronic effects on reproduction accounted for 78.92%. Mixtures of benzene, trichloroethylene, and toluene had effects at concentrations below their individual LOELs. Observed effects of 20/24 mixtures tested fell within the 95% prediction interval for a concentration-addition model of joint action derived from tests with individual components. However, the observed response differed significantly from the predictive relationship. In general, the predictive relationship overestimated mixture toxicity. Fitted relationships reduced observed error by as much as 82% compared to the predictive model.

Animals↗
PubMed1978

Changes of sensitivity to the cuing properties of narcotic drugs as evidenced by generalization and cross-generalization experiments.

With a discrete-trial, food-reward, two-lever procedure, rats were trained to discriminate 0.04 mg/kg fentanyl from saline. Individual threshold doses for generalization of fentanyl and for cross-generalization of morphine were determined repeatedly during a 17-week posttraining period. Threshold doses of both drugs almost continuously shifted in both the up- and downward direction. Shifts of fentanyl threshold doses covaried with those of morphine threshold doses. These shifts can best be described by a sustained oscillation, the mean amplitude of which amounts to a factor 3.65 of the dose-range for fentanyl, and to a factor 1.85 for morphine. The upper and lower limits of oscillation were symmetrical with respect to baseline. The oscillation can be described by a function expressing that the more distant a point along the function is from the baseline, the more it is susceptible to (positive/negative) acceleration along the intensity (i.e., dose) axis.

Animals↗
PubMed1978

Generalization study with some narcotic and nonnarcotic drugs in rats trained for morphine-saline discrimination.

Rats were trained to lever-press on an FR-10 schedule for food reinforcement, and to respond differentially on two levers while discriminating the effects of morphine (10 mg/kg) injection from those of saline (1 ml/kg). Following discrimination training, the morphine stimulus was generalized to propoxyphene, methadone, fentanyl, and sulfentanyl in a dose-dependent manner, and saline was generalized to alcohol, pentobarbital, azaperone, clonidine, naloxone, and p-chloroamphetamine. p-Chloroamphetamine failed to block the morphine stimulus.

Animals↗