Transdemal Delivery of Opioid Antagonist Prodrugs

A composition, a method and an apparatus for transdermally delivering an effective amount of opioid antagonists derived from prodrugs for treatment of eating disorders, narcotic dependence and alcoholism. In addition, the present invention relates to a composition, a method and an apparatus for transdermally delivering an effective amount of an opioid and opioid antagonist derived from an opioid agonist and one of an opioid antagonist and a prodrug for treatment of pain

Delivery System for a Composition

Devices and methods for cutaneous delivery of a composition are provided, wherein the composition is passed through an ordered nanoporous membrane in fluid communication with a reservoir. The nanoporous membrane includes a plurality of aligned hollow nanotubules coated with a continuous polymer matrix, and etched to open the plurality of hollow nanotubules and form pores. In one embodiment, the etching step oxidizes an end of the nanotubules to form carboxylate groups. The ordered nanoporous membrane further includes at least one additional functional unit bound to the carboxylate groups. The at least one additional functional unit selectively exposes or at least partially occludes the pore of an adjacent nanotubule, thereby controlling flux rate through the membrane. In one embodiment, application of an electrical impulse to the membrane causes the at least one additional functional unit to selectively expose or at least partially occlude the pore

Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration

Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs). The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs), and then evaluated the efficacy of fatty acid amide hydrolase (FAAH) inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the entorhinal cortex and hippocampus following two days, but not four days, of treatment. Furthermore, binge alcohol treatment did not change the tissue content of the three NAEs quantified, including the endocannabinoid and anandamide. In a separate study, the FAAH inhibitor, URB597 was administered to rats during alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB) staining. The administration of URB597 during binge treatment did not significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however, a follow up “target engagement” study found that NAE augmentation by URB597 was impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by FAAH inhibition

Enhancing Transdermal Delivery of Opioid Antagonists and Agonists Using Codrugs Linked To Bupropion or Hydroxybupropion

The present invention is directed to novel codrugs comprising bupropion or hydroxybupropion and an opioid antagonist or an opioid agonist joined together by chemical bonding. The codrugs provide a significant increase in the transdermal flux across human skin, as compared to the basic opioid antagonist or opioid agonist

Carbon Nanotube Membranes for Use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT) membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual\u27s needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse

Quantification of anandamide, oleoylethanolamide and palmitoylethanolamide in rodent brain tissue using high performance liquid chromatography–electrospray mass spectroscopy

AbstractReported concentrations for endocannabinoids and related lipids in biological tissues can vary greatly; therefore, methods used to quantify these compounds need to be validated. This report describes a method to quantify anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) from rodent brain tissue. Analytes were extracted using acetonitrile without further sample clean up, resolved on a C18 reverse-phase column using a gradient mobile phase and detected using electrospray ionization in positive selected ion monitoring mode on a single quadrupole mass spectrometer. The method produced high recovery rates for AEA, OEA and PEA, ranging from 98.1% to 106.2%, 98.5% to 102.2% and 85.4% to 89.5%, respectively. The method resulted in adequate sensitivity with a lower limit of quantification for AEA, OEA and PEA of 1.4ng/mL, 0.6ng/mL and 0.5ng/mL, respectively. The method was reproducible as intraday and interday accuracies and precisions were under 15%. This method was suitable for quantifying AEA, OEA and PEA from rat brain following pharmacological inhibition of fatty acid amide hydrolase

A Solubility and Related Physicochemical Property Comparison of Buprenorphine and Its 3-Alkyl Esters

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41440/1/11095_2004_Article_307028.pd