Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topical formulations of tetracaine in vehicles of propylene glycol and saline are tested on human volunteers with standard occlusive, adhesive, transdermal patches. The effects of formulation composition, dose, and onset time are investigated. Dose-response studies indicate that the optimum formulation for the diffusion of tetracaine in vivo is 60% free base and 40% acid salt (w/w) in 40% propylene glycol and 60% saline (v/v). A concentration of 0.3 M [8.3% (w/v)] tetracaine is sufficient to reach the dose plateau. Time-response studies indicate that high concentrations of tetracaine in the optimum formulation [1.1 and 1.8 M, 30 and 50% (w/v), respectively] can produce statistically significant analgesia relative to a placebo after 45 min. Comparison of these in vivo data with earlier in vitro data indicate that the optimum formulation with regard to clinical studies is identical to that for in vitro diffusion through hairless mouse skin [60% free base and 40% acid salt (w/w) in 40% propylene glycol and 60% saline].
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PMID:Evaluation of local anesthesia provided by transdermal patches containing different formulations of tetracaine. 828 25

The present experiments were initiated to study the effects of morphine, nefopam and paracetamol in the naked mole-rat, a hairless rodent that lives in subterranean colonies of up to 300, following the inability to demonstrate morphine analgesia in the hot-plate test in the rodent. The formalin test was used. Injection of 20 microliters 10% formalin produced two periods of high licking and pain behaviour, the early (0-5 min) and the late phase (15-60 min). Morphine (10 or 20 mg/kg), nefopam (10 or 20 mg/kg) and paracetamol (200 mg/kg) significantly inhibited the two phases. Paracetamol (400 mg/kg) produced significant analgesia only during the late phase. It is concluded that, unlike in the hot-plate test, it is possible to demonstrate the analgesic effects of morphine in the naked mole-rat, in the formalin test.
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PMID:The formalin test in the naked mole-rat (Heterocephalus glaber): analgesic effects of morphine, nefopam and paracetamol. 842 79

Skin electroporation has recently been shown to increase transdermal transport of small-size drugs as well as considerably larger molecules by up to 4 orders of magnitude in vitro. Nevertheless, no in vivo studies have proven that high-voltage pulses can induce therapeutic plasma levels of drug. The aim of the present report was precisely to study the potential of skin electroporation in transdermal delivery of fentanyl in vivo. Fentanyl was transdermally delivered to hairless rats using high-voltage pulsing. Following the administration, the pharmacokinetics and pharmacodynamics were assessed. Significant fentanyl plasma concentrations were rapidly achieved using skin electroporation. Immediately after the 5 min pulsing, fentanyl plasma levels reached one third of the maximal plasma concentration of approximately 30 ng/ml, the peak occurring 30 min after the electroporation. Deep analgesia and supraspinal effects were achieved, antinociception lasting for an hour. The magnitude of the effects was, however, dependent on the electrical parameters of the pulses.
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PMID:Transdermal delivery of fentanyl: rapid onset of analgesia using skin electroporation. 968 89

The tolerance to analgesia and dependence liability of dihydroetorphine following topical application were investigated in hairless rats with and without formalin-induced inflammation. The analgesic effect of dihydroetorphine (s.c.) was 4600- to 7200-fold more potent than that of morphine. In non-inflamed rats, the analgesic effect of 24-h topical application of dihydroetorphine tape (35 microg) and 4-day repeated tape applications (20 microg/5 h/day) decreased with time after the start of application, even though the plasma dihydroetorphine concentrations did not decrease. In formalin-inflamed rats, however, the tolerance to analgesia diminished. Naloxone-precipitated weight loss was observed after 24-h infusion of dihydroetorphine but not after the tape application in non-inflamed rats. A significant rewarding effect was found in the non-inflamed rats conditioned by s.c. injection and tape application but not in the formalin-inflamed rats. These results indicate that topical application of dihydroetorphine has a tolerance and dependence liability when there is no pain, and therefore, it should be used only for pain relief.
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PMID:Tolerance to analgesia and dependence liability by topical application of dihydroetorphine to hairless rats. 1144 80

Previous studies have demonstrated that delta9-tetrahydrocannabinol (THC) enhances the antinociceptive potency of many opioids administered by a variety of different routes of administration. We hypothesized that THC would enhance fentanyl or buprenorphine analgesia via the transdermal route of administration. THC was first demonstrated to enhance opioid antinociception when both drugs were administered parenterally in a hairless guinea pig model using the pin prick test. A low dose of THC (50 mg/kg, i.p.) produced no antinociception. However, THC enhanced the potency of s.c. fentanyl by 6.7-fold, and s.c. buprenorphine in a non-parallel fashion. For the transdermal studies, THC, fentanyl or buprenorphine was applied by pipette to the skin of the dorsum between the fore- and hind-flanks and covered with individual Tegederm patches. THC (400 mg/kg) produced no antinociception. However, THC enhanced fentanyl's potency by 3.7-fold at 2-h, and 5.8-fold at 4-h. Buprenophine's potency was increased 8.2-fold at 2-h and 7.2-fold at 4-h when co-administered with THC. These results indicate that the enhancement of transdermal opioids by THC could lead to the design of an effective combination analgesic patch.
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PMID:Enhancement of transdermal fentanyl and buprenorphine antinociception by transdermal delta9-tetrahydrocannabinol. 1628 38