ALGRX 4975 is capsaicin for injection. Subjects with lateral epicondylitis of less than three months duration received a single injection of ALGRX 4975, 100 μg in 0.5 ml, or placebo, 0.5 ml, at the site of maximum tenderness 10 minutes following lidocaine, 250 mg in 2.5 ml. The primary efficacy endpoint was pain on resisted wrist dorsiflexion, defined as 0= no pain on resisted dorsiflexion, 1= full range of motion with slight pain, 2= moderate, and 3= marked pain on dorsiflexion, and 4= dorsiflexion not possible due to pain. Among the 22 subjects who received ALGRX 4975, 17 (77.3%) experienced category 3 or 4 pain on dorsiflexion at baseline, compared to 13 of the 23 subjects (56.5%) in the placebo group (p= 0.14); no subject in either group had scores of 0 or 1. Responders were defined as those subjects with scores of 0 or 1 following injection. Responders at the end of weeks 1, 2, and 4 following the single injection of ALGRX 4975 or placebo were 12 (54.5%) compared to 3 (13%), p= 0.0056, 11 (50%) compared to 4 (17.4%), p=0.0150, and 14 (63.6%) compared to 7 (30.4%), p=0.0256, respectively. Secondary endpoints of pain (NRS) and tenderness elicited by investigator were statistically significantly (p<0.05) less in the ALGRX 4975 group at the end of weeks 1, 2, and 4. Subject’s global impression of change was significantly (p<0.05) greater at the end of weeks 1, 2, and 4 in the ALGRX 4975 group compared to placebo. ALGRX 4975 injection was associated with transient pain on injection, but was otherwise well-tolerated. A single injection of ALGRX 4975, 100 μg, was associated with less pain and increased function during a four week observation period in subjects with acute lateral epicondylitis.

To determine the role of CCK-A receptors in the cholecystokinin (CCK)-induced suppression of locomotor activity in the rat, the ability of the selective CCK-A receptor antagonist L364,718 to block these responses was investigated. Cholecystokinin octapeptide (CCK8) (10,100 μg/kg IP) and caerulein (1, 5, 10 μg/kg IP) produced marked reductions in locomotor activity whereas cholecystokinin tetrapeptide (CCK4) (100 μg/kg IP) was without effect. The reductions in activity produced by CCK8 (10 μg/kg) and caerulein (10 μg/kg) were antagonized by L364,718 (100 μg/kg IP). In an open field test CCK8 (10 μg/kg IP) reduced locomotor activity and total number of rears and increased pause duration. These effects of CCK8 on open-field behaviour were also antagonized by L364,718 (100 μg/kg IP). It is concluded that L364,718 is a potent antagonist of the actions of CCK8 and caerulein on locomotor activity, suggesting that the effects of these peptides are mediated by a CCK-A receptor.

Annals of the New York Academy of SciencesVolume 575, Issue 1 p. 525-528 Which Subtype(s) of 5-HT Receptor Mediates the Anorectic Effects of Drugs That Act via the 5-HT System? G. HEWSON, G. HEWSON Parke-Davis Research Unit Hills Road Cambridge, CB2 2QB, United KingdomSearch for more papers by this authorG. E. LEIGHTON, G. E. LEIGHTON Parke-Davis Research Unit Hills Road Cambridge, CB2 2QB, United KingdomSearch for more papers by this authorR. G. HILL, R. G. HILL Parke-Davis Research Unit Hills Road Cambridge, CB2 2QB, United KingdomSearch for more papers by this authorJ. HUGHES, J. HUGHES Parke-Davis Research Unit Hills Road Cambridge, CB2 2QB, United KingdomSearch for more papers by this author G. HEWSON, G. HEWSON Parke-Davis Research Unit Hills Road Cambridge, CB2 2QB, United KingdomSearch for more papers by this authorG. E. LEIGHTON, G. E. LEIGHTON Parke-Davis Research Unit Hills Road Cambridge, CB2 2QB, United KingdomSearch for more papers by this authorR. G. HILL, R. G. HILL Parke-Davis Research Unit Hills Road Cambridge, CB2 2QB, United KingdomSearch for more papers by this authorJ. HUGHES, J. HUGHES Parke-Davis Research Unit Hills Road Cambridge, CB2 2QB, United KingdomSearch for more papers by this author First published: December 1989 https://doi.org/10.1111/j.1749-6632.1989.tb53282.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume575, Issue1The Psychobiology of Human Eating Disorders: Preclinical and Clinical PerspectivesDecember 1989Pages 525-528 RelatedInformation

1. To determine the role of endogenous cholecystokinin (CCK) in the regulation of food intake, the effects of the potent CCK receptor antagonist L364,718 were investigated on the intake of a palatable diet in non-deprived rats. The effect of a single dose of proglumide was also investigated for comparative purposes. In addition, the ability of L364,718 to antagonize the reduction in food intake produced by exogenous cholecystokinin-octapeptide (CCK8) or bombesin in food-deprived rats was determined. 2. L364,718 (10-100 micrograms kg-1, i.p.) increased the intake of palatable diet during the 30 min test period. Proglumide (300 mg kg-1, i.p.) also increased the intake of palatable diet. Conversely, CCK8 (0.5-5 micrograms kg-1, i.p.) produced a reduction in the intake of the diet. 3. In fasted rats, L364,718 (100 micrograms kg-1, i.p.) antagonized the reduction in food intake produced by CCK8 (10 micrograms kg-1, i.p.) but not that produced by bombesin (50 micrograms kg-1, i.p.). L364,718 did not increase food intake in these animals when measured over a 6 h period. 4. It is concluded that L364,718 is a potent, selective antagonist of the effects of CCK8 on food intake. The observation that L364,718 and proglumide increase the intake of a palatable diet provides some evidence that endogenous CCK is involved in the control of food intake in this model.

1. To determine which subtype(s) of 5-hydroxytryptamine (5-HT) receptor are involved in the anorectic action of quipazine, the ability of selective antagonists at 5-HT2- and 5-HT3-receptors, and an antagonist at 5-HT1-like receptors, to block this response were investigated in non-deprived rats, trained to eat a palatable diet. 2. Quipazine (0.5-8 mg kg-1, i.p.) produced a dose-related reduction in the intake of palatable diet. 3. The anorectic effect of 4 mg kg-1 quipazine was antagonized by the nonselective 5-HT-receptor antagonist methysergide (5 mg kg-1, i.p.) and by the selective 5-HT2-receptor antagonists ketanserin (1 mg kg-1 and 2.5 mg kg-1, i.p.) and ritanserin (0.5 mg kg-1 and 1 mg kg-1, i.p.). The selective 5-HT3-receptor antagonist GR38032F (1 mg kg-1, i.p.) and (-)-pindolol (4 mg kg-1, i.p.), which blocks some of the effects mediated at 5-HT1-like receptors, did not block the reduction in food intake produced by this dose of quipazine. 4. None of the 5-HT-receptor antagonists had any effect on food intake when they were administered alone, suggesting that endogenous 5-HT is not involved in the tonic control of food intake under the conditions of these experiments. 5. It is concluded that the anorectic action of quipazine is mediated, at least in part, by activation of 5-HT2-receptors.

To determine the role played by 5-HT2 receptors in the anorectic action of DL-fenfluramine, the ability of the selective 5-HT2 receptor antagonist ketanserin to block the reduction in food intake produced by this drug was investigated in non-deprived rats. Ketanserin (1 and 2.5 mg/kg i.p.) produced a dose-dependent antagonism of the anorectic effect of DL-fenfluramine (3 mg/kg i.p.). Prazosin (1 mg/kg i.p.) did not antagonise this effect. It is concluded that the anorectic actions of DL-fenfluramine are mediated via 5-HT2 receptors.

The effects of the selective kappa opioid receptor agonists PD 117302 [(±)trans-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl-]benzo-[b]-thiophene-4-acetamide] and U50488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide) were investigated on food intake in non-deprived rats over a 24 hr period following subcutaneous administration. At doses of 2.5 mg/kg and 5 mg/kg, both PD 117302 and U50488 initially increased food intake. Between 6–24 hr, however, PD117302 (2.5–10 mg/kg) and U50488 (2.5 mg/kg and 5 mg/kg) caused a reduction in food intake. The largest doses of PD117302 and U50488 also reduced total 24 hr food intake. The reduction in food intake produced by PD117302 (5 mg/kg) was selective, since the intake of water was not affected. It is concluded that the kappa agonists PD117302 and U50488 produce a biphasic effect on 24 hr food intake, with an initial hyperphagia followed by a decrease in food intake.

The effects of four anilidopiperidine analgesics, fentanyl, sufentanil, lofentanil and alfentanil on the activity of single neurones in the rat brain stem were examined using the technique of microiontophoresis. Neurones whose discharge rate could be related to respiration and non-respiratory neurones were studied. Alfentanil produced depression of neuronal firing which was slow in onset, shallow and prolonged, similar to the responses seen previously with etorphine. These responses were antagonised by naloxone. The depressant responses to fentanyl, sufentanil, and lofentanil were often different in character, being rapid in onset and of short duration, although slow long lasting responses also occurred and sometimes the two responses were combined. However, only the slow response was blocked by naloxone, the fast, short-duration response being naloxone-resistant. No differences in the responses of respiratory and non-respiratory neurones to these drugs were observed.