naloxone and Flushing

Topics: Animals; beta-Endorphin; Biomechanical Phenomena; Chlorpropamide; Dogs; Eating; Endocrine Glands; Endorphins; Enkephalins; Ethanol; Flushing; Guinea Pigs; Humans; Islets of Langerhans; Male; Morphine; Naloxone; Pancreas; Pancreatic Hormones; Peptides; Protein Precursors; Rats; Sheep

To investigate whether the introduction of methadone into the skin of the human forearm produces wheals, cutaneous vasodilatation or thermal hyperalgesia and, if so, to determine whether these responses are mediated by opioid receptors.. Healthy adults.. In Experiment 1 (N = 11), the increase in local blood flow (monitored with a laser Doppler flowmeter) was greater after the iontophoresis of methadone than saline (mean increase +/- S.D. 12.6 +/- 8.8 versus 2.2 +/- 1.9 times greater than baseline, p < 0.01). Flushing did not spread into surrounding skin and wheals did not form. In Experiment 2, pre-treatment with naloxone (N = 12) prevented increases in blood flow to methadone whereas saline pre-treatment (N = 14) did not. The heat pain threshold was lower at the site of methadone administration than at an untreated site (42.8 +/- 2.3 degrees C versus 44.6 +/- 1.7 degrees C, p < 0.001), and this effect was inhibited by naloxone pre-treatment. However, naloxone pre-treatment also antagonized an inhibitory effect of methadone on the pain generated by a 7-second pulse of 45 degrees C heat. In Experiment 3 (N = 11), the iontophoresis of methadone was repeated after an interval of 1.5 h. Vasodilatation to methadone persisted after the second iontophoresis, and sensitivity to heat was greater at a site of methadone administration than at a site of saline administration or an untreated control site.. Stimulation of mu-opioid receptors dilated cutaneous blood vessels, and evoked local thermal analgesia and hyperalgesia at different stimulus intensities. However, stimulation of mu-opioid receptors did not produce wheals or flares.

Topics: Administration, Cutaneous; Adolescent; Adult; Female; Flushing; Hot Temperature; Humans; Hyperalgesia; Iontophoresis; Male; Methadone; Middle Aged; Naloxone; Pain; Pain Measurement; Regional Blood Flow; Skin

The neuroendocrine and clinical effects of transdermal 17 beta-estradiol (rated at 50 micrograms/day; TTS 50) were studied in 40 postmenopausal women; ten additional postmenopausal women did not receive any drugs. The changes in LH and rectal temperature induced by the infusion of the opioid antagonist naloxone (10 mg i.v. bolus plus 10 mg/h for 4 h) were used to evaluate the central activity of endogenous opioid peptides. TTS 50 increased opioid activity, as evidenced by the restoration of the LH response (P less than 0.01) and the enhancement of the hypothermic effect (P less than 0.05) of naloxone. A greater reduction in hot flushes was observed in TTS 50-treated subjects than in untreated women, with the maximal effect of TTS 50 achieved after 3 months of therapy. TTS 50 did not modify the concentrations of circulating lipids, glucose or liver enzymes but reduced the biochemical parameters indicative of bone reabsorption. Bone density of the distal radius significantly increased during TTS 50 (P less than 0.02), reaching its maximum value after 6 months of therapy. Thereafter bone density declined, but more slowly than in untreated women. Our data suggest that TTS 50 has marked neuroendocrine effects, that it diminishes the incidence of hot flushes and reduces bone demineralization. By contrast, it has a very little, if any, metabolic impact on the liver or on glucose and lipid metabolism.

Topics: Administration, Cutaneous; Adult; Alkaline Phosphatase; Body Temperature; Bone Density; Calcium; Estradiol; Estrogen Replacement Therapy; Estrone; Female; Flushing; Follicle Stimulating Hormone; Humans; Lipids; Luteinizing Hormone; Menopause; Middle Aged; Naloxone; Progesterone; Prolactin

The effects of ethanol and subsequent administration of intravenous naloxone were studied in double-blind, placebo-controlled fashion with a group of six male chlorpropamide alcohol flushers (CPAF) and a group of 13 nonflushing males. The effect of ethanol intoxication on fine motor control was measured by a typing test. When sober, the two groups performed in comparable fashion. When intoxicated, the CPAF group displayed significantly greater impairment than the nonflushing group as measured by typing errors committed in 3 min (CPAF: 55.4 +/- 10.1 errors, n = 12; vs. nonflushing: 15.6 +/- 2.3, n = 32; p = 0.0000015 by Student's unpaired t test). Chlorpropamide alcohol flushers appeared to be more sensitive to ethanol. Naloxone reversed this effect for individuals in the CPAF group (saline treatment: 51.0 +/- 11.7 errors per minute; vs. naloxone treatment: 23.7 +/- 4.2; p = 0.034 by Student's paired t test, n = 6). Naloxone had no effect in the nonflushing group. Unlike the normal, nonflushing group, the CPAF group demonstrated an increased sensitivity to ethanol that was partially antagonized by naloxone.

Topics: Adult; Alcoholic Intoxication; Chlorpropamide; Double-Blind Method; Ethanol; Flushing; Humans; Male; Motor Skills; Naloxone

The effects of naloxone and a met-enkephalin analogue on head pain, vascular responses, and autonomic-associated symptoms were studied in 24 migraine patients, 12 patients suffering from tension-type headache, and 24 normal subjects in whom headache was induced by intravenous injections of increasing doses of histamine (histamine test). A hypersensitivity to histamine was found in migraine patients. Naloxone slightly increased the intensity of pain in migraine and tension-type headache sufferers. The met-enkephalin analogue did not affect the intensity of pain in migraine patients, tension-type headache patients, and normal subjects, but it reduced the intensity and duration of facial flushing (p less than 0.001) and the autonomic symptoms (p less than 0.001) in migraine patients when the pretreatment was not given shortly before histamine. In migraine patients, there seems to be an increased reactivity (receptor supersensitivity?) to the met-enkephalin analogue at the level of systems that inhibit facial vasodilatation and autonomic symptoms.

Topics: Adult; Autonomic Nervous System; Enkephalin, Methionine; Female; Flushing; Headache; Histamine; Humans; Male; Migraine Disorders; Naloxone; Pain Measurement

A 77-yr-old man presented with severe episodes of hypotension, flushing and sweating starting immediately after infarcting his only remaining functioning testis. The attacks were shown to be mediated by the cervical sympathetic chain, the reaction on the face and neck being abolished by a stellate ganglion block. The severity and frequency of sweating was also considerably reduced with naloxone as may be seen in female climacteric flushing. Injection of testosterone significantly reduced the frequency and severity of the attacks, which were unaltered by oestrogen treatment.

Topics: Aged; Autonomic Nerve Block; Flushing; Ganglia, Sympathetic; Humans; Infusions, Parenteral; Male; Naloxone; Sweating; Testosterone

The response of plasma immunoreactive met-enkephalin (IR-met-enkephalin) to ethanol (8 g by mouth) after chlorpropamide (250 mg daily for 14 d) was studied in three groups of non-insulin dependent diabetics (a) six diabetics who showed chlorpropamide alcohol flush (CPAF) and in whom the reaction could be blocked by indomethacin, (b) five diabetics who showed CPAF but in whom the flush could not be blocked by indomethacin and (c) five diabetics who did not show CPAF. A rise in plasma IR-met-enkephalin was observed in all three groups. When the two groups of flushers were re-tested with the addition of an infusion of naloxone a rise in plasma IR-met-enkephalin was still demonstrated in both groups regardless of whether the flush was blocked by naloxone. Naloxone blocked the flush only in those six subjects whose flush could be blocked by indomethacin. In five subjects, all flushers, CPAF was tested using intravenous and oral ethanol in doses producing similar plasma ethanol levels. A facial flush was induced by both intravenous and oral ethanol. In three flushers, plasma IR-met-enkephalin levels were measured during CPAF testing with both intravenous and oral ethanol. None showed a rise in plasma IR-met-enkephalin after intravenous ethanol, despite the appearance of a facial flush, whereas all showed a rise after oral ethanol. We therefore conclude that CPAF is unlikely to be caused by a rise in plasma IR-met-enkephalin.

Topics: Administration, Oral; Adult; Aged; Chlorpropamide; Diabetes Mellitus, Type 2; Drug Interactions; Enkephalin, Methionine; Ethanol; Female; Flushing; Humans; Indomethacin; Injections, Intravenous; Male; Middle Aged; Naloxone