Neonatal treatment of rats with Monosodium Glutamate (MSG) has been demonstrated to destroy cell bodies of neurons in the arcuate nucleus including the brain beta-endorphin (B-END) system. The effects on opiate receptors of the loss of B-END is unknown. Seven to nine month old rats treated with MSG on the first two postnatal days and litter matched untreated control rats were decapitated and th...

1. Tramadol analgesic causes respiratory depression that is mainly mediated by opioid receptors. However, Tramadol is a weak opioid receptor agonist, and its metabolites O-desmethyltramadol is only about 1/10 of morphine, and fentanyl is a strong opioid receptor agonist, its potency is about 100 times morphine. When the two together, to be a major contributor to opioid receptors is fentanyl. Pr...

Numerous rather than a few analgesic endogenous neuropeptides are likely to work in concert in vivo in ameliorating pain. Identification of effective neuropeptide combinations would also facilitate the development of gene or cell-based analgesics. In this study, opioid peptides endomorphin-1 (EM-1) and endomorphin-2 (EM-2) and the peptide histogranin analogue [Ser(1)]histogranin (SHG), which po...

Guanine nucleotides regulate binding of opiate agonists to membrane receptors by increasing agonist dissociation rates. The current study demonstrates that the ability of guanosine 5'-triphosphate (GTP) and its nonhydrolyzable analogue guanylyl-5'-imidodiphosphate (Gpp(NH)p) to inhibit opiate agonist binding to rat brain membranes can be altered by two methods: by preincubating with EDTA, and b...

BACKGROUND Ranitidine (Zantac®) is a H2-receptor antagonist commonly used for the treatment of acid-related gastrointestinal diseases. Ranitidine was reported to be a substrate of the organic cation transporters OCT1 and OCT2. The hepatic transporter OCT1 is highly genetically variable. Twelve major alleles confer partial or complete loss of OCT1 activity. The effects of these polymorphisms are...

BACKGROUND Opioid-induced respiratory depression is antagonized effectively by the competitive opioid receptor antagonist naloxone. However, to fully understand the complex opioid agonist-antagonist interaction, the effects of various naloxone doses on morphine and morphine-6-glucuronide (M6G)-induced respiratory depression were studied in healthy volunteers. METHODS Twenty-four subjects rece...

We have previously reported the chemistry and antinociceptive properties of a series of glycosylated enkephalin analogs (glycopeptides) exhibiting approximately equal affinity and efficacy at δ opioid receptors (DORs) and μ opioid receptors (MORs). More detailed pharmacology of the lead glycopeptide MMP-2200 [H₂N-Tyr-D-Thr-Gly-Phe-Leu-Ser-(O-β-D-lactose)-CONH₂] is presented. MMP-2200 produced d...

The nonopioid actions of spinal dynorphin may promote aspects of abnormal pain after nerve injury. Mechanistic similarities have been suggested between opioid tolerance and neuropathic pain. Here, the hypothesis that spinal dynorphin might mediate effects of sustained spinal opioids was explored. Possible abnormal pain and spinal antinociceptive tolerance were evaluated after intrathecal admini...

Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient's sel...

Opioid-induced constipation is a major side effect that persists with long-term opioid use. Previous studies demonstrated that nicotine-induced contractions are enhanced after long-term morphine exposure in guinea pig ileum. In the present study, we examined whether the increased sensitivity to nicotine could be observed in single enteric neurons after long-term morphine exposure, determined th...