DALDA (H-Tyr-D-Arg-Phe-Lys-NH(2)) and [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)) (Dmt = 2',6'-dimethyltyrosine) are potent and highly selective mu-opioid agonists (K(i)(delta)/K(i)(mu) > 10,000 and K(i)(kappa)/K(i)(mu) > 100). Both peptides carry a 3+ charge at physiological pH. Their antinociceptive and respiratory effects were compared with morphine (MOR) after intrathecal administration in ra...

This is the first study designed to compare the pattern of stimulation of c-Fos in selected brain structures after an acute administration of morphine and methadone. Methadone and morphine induced activation of c-Fos protein in the terminal forebrain projecting areas of the brain dopaminergic system, i.e. the striatum and nucleus accumbens. Taking into account generally accepted differences in ...

Background: Morphine and clonidine show synergy or antagonism inhibiting gastrointestinal transit depending on their proportion and level of effect. Their interaction during morphine tolerance and intestinal inflammation were assessed. Methods: Gastrointestinal transit in mice was evaluated with charcoal and antitransit effects expressed as percent mean values f SEM. Tolerance was induced with ...

Levorphanol (levo-3-hydroxy-N-methylmorphinan) is a step 3 opioid first developed in the 1940s as an alternative to morphine. Levorphanol belongs to the morphinan opioid series. Levorphanol has greater potency than morphine and is a potent N-methyl-d aspartate (NMDA) antagonist. Levorphanol interferes with the uptake of norepinephrine and serotonin, which makes it potentially useful for neuropa...

In searching for an analgesic with fewer side effects than morphine, examination of morphine's active metabolite, morphine-6-glucuronide (M6G), suggests that M6G is possibly such a drug. In contrast to morphine, M6G is not metabolized but excreted via the kidneys and exhibits enterohepatic cycling, as it is a substrate for multidrug resistance transporter proteins in the liver and intestines. M...

UNLABELLED Methadone is a synthetic opioid analgesic that is used as an alternate to morphine and hydromorphone for patients with severe pain. It is increasingly being used in opioid rotation schedules. Methadone has an asymmetric carbon atom resulting in 2 enantiomeric forms, the d and l isomers. The racemic mixture (dl-methadone) is the form commonly used clinically. Recent studies have revea...

BACKGROUND Children and infants with impaired swallow or compromised enteral absorption require alternative routes for administration of analgesia. Recent clinical guidance and practice for paediatric palliative care teams, who often treat such children, supports buccal morphine sulphate as a fast acting, effective and easily administered agent for pain relief. However, a consideration of the p...

The periaqueductal gray (PAG) is involved in many gonadal steroid-sensitive behaviors, including responsiveness to pain. The PAG projects to the rostral ventromedial medulla (RVM), comprising the primary circuit driving pain inhibition. Morphine administered systemically or directly into the PAG produces greater analgesia in male compared to female rats, while manipulation of gonadal hormones a...

Pain is a distressing symptom of cancer that affects the quality life patients, families, and caregivers. Moderate to severe pain common throughout disease trajectory cancer, its prevalence increases course illness, it has been reported in 59% patients undergoing anticancer treatment, 64% those with advanced/metastatic 33% having completed curative treatment. Adequate management cornerstone for...