Studies were designed to investigate differences in pharmacokinetics and pharmacodynamics of the adenosine A1 receptor agonist N-(p-sulfophenyl)adenosine (SPA) between lean and obese Zucker rats. In conscious rats, time courses of the effect on heart rate and parameters of lipid metabolism (fatty acids, glycerol) were monitored in combination with the decline of drug concentrations after i.v. a...

In this study, the activity of the d-opioid receptor subtypeselective agonist, SB 227122, was investigated in a guinea pig model of citric acid-induced cough. Parenteral administration of selective agonists of the d-opioid receptor (SB 227122), m-opioid receptor (codeine and hydrocodone), and k-opioid receptor (BRL 52974) produced dose-related inhibition of citric acid-induced cough with ED50 v...

-Hydroxybutyrate (GHB) is a psychotropic compound endogenous to the brain. Despite its potentially great physiological significance, its exact molecular mechanism of action is unknown. GHB is a weak agonist at GABAB receptors, but there is also evidence of specific GHB receptor sites, the molecular cloning of which remains a challenge. Ligands with high affinity and specificity for the reported...

The objective of this study was the construction of a pharmacokinetic-pharmacodynamic model to describe the effects of chlorprothixene on prolactin secretion and the time-dependent alterations in the concentration-effect relationship due to tolerance development. Prolactin and chlorprothixene serum concentrations were determined in eight healthy men for up to 72 h after the intravenous and oral...

Pharmacological and behavioral studies suggest that spinal and -opioid antinociceptive systems are functionally associated with ovarian sex steroids. These interactions can be demonstrated specifically during pregnancy or hormone-simulated pregnancy (HSP). The analgesia associated with both conditions can be abolished by blockade of either spinal -opioid receptors or -opioid receptors (DOR). Fu...

Amiodarone (AM) is an efficacious antidysrhythmic agent that can cause numerous adverse effects, including potentially lifethreatening pulmonary fibrosis. The current study was undertaken to investigate potential protective mechanisms of vitamin E against AM-induced pulmonary toxicity (AIPT) in the hamster. Three weeks after intratracheal administration of AM (1.83 mol), increased pulmonary hyd...

19,19-Dimethylheptyl-D-8-tetrahydrocannabinol-11-oic acid (CT-3) is a novel cannabinoid that is under development by Atlantic Pharmaceuticals as an anti-inflammatory and analgesic drug. The objective of the study was to investigate the effects of CT-3 on overt symptom complex (Irwin’s test), nociception, gastrointestinal (GI) ulceration, and pharmacological availability after intragastric (i.g....

In analgesic drug development, preclinical procedures are widely used to assess drug effects on pain-related behaviors. These procedures share two principal components: 1) a manipulation intended to produce a pain-like state in the experimental subject and 2) measurement of behaviors presumably indicative of that pain state. Drugs can then be evaluated for their ability to attenuate pain-relate...

Both the histamine H1-receptor (H1R) and H2-receptor (H2R) exhibit pronounced species selectivity in their pharmacological properties; i.e., bulky agonists possess higher potencies and efficacies at guinea pig (gp) than at the corresponding human (h) receptor isoforms. In this study, we examined the effects of N-acylated imidazolylpropylguanidines substituted with a single phenyl or cyclohexyl ...

Previous research has shown that compounds with mixed and activity may have utility for the treatment of cocaine abuse and dependence. The present study characterizes the pharmacological profile of a bivalent morphinan that was shown to be a opioid receptor agonist and a opioid receptor agonist/antagonist. MCL-145 [bis(N-cyclobutylmethylmorphinan) fumarate] is related to the morphinan cyclorpha...