Biomedical subjects

C W Gowdey

Publications and source records attributed to C W Gowdey.

At least 37 records · Page 2Linked to original sources

PubMed1978

Spontaneous hydrolysis of heroin in buffered solution.

Electron-capture gas-liquid chromatography was used to study the spontaneous hydrolysis of heroin in phosphate buffer (pH 6.4 and pH 7.4) at 23 degrees C. Aliquots of solution were taken over a 24-h period. After extraction at pH 8.9 into propan-2-ol (10%)-ethyl acetate, deacetylated products were made into hepafluorobutyrate derivatives which were analyzed quantitatively using nalorphine as the internal standard. Heroin decomposes to 06-monoacetylmorphine (06-MAM) under these conditions. Further decomposition to morphine was not observed. Spontaneous hydrolysis was faster at pH 7.4 (first-order rate constant, 9.6 x 10-5 min-1) than at pH 6.4 (first-order rate constant, 3.0 x 10-5 min-1). In 24 h, the decomposition to 06-MAM was 13 and 4%, respectively.

Chromatography, Gas↗

PubMed1978

Measurement of diurnal core temperatures of rats in operant cages by AM telemetry.

A special AM telemetric system of recording core temperature was developed for rats working in individual, adjacent operant conditioning chambers within a sound-attenuated room. The system monitored core temperatures of each rat continuously and recorded them, in degrees Celsius, every 30 min so that diurnal patterns and fluctuations after saline or drug injections could be determined. Periodic comparisons showed close agreement with temperatures recorded by a rectal probe.

Animals↗

PubMed1978

Analgesia duration and physical dependence in mice after a single injection of three heroin salts and morphine sulphate in various vehicles.

Mice were given single s.c. injections of morphine sulphate (M.S.), heroin hydrochloride (H.HCl) and the sparingly-soluble diheroin pamoate (H.Pam) and 3,5-di-tert-butyl-2,6-dihydroxybenzoate (H.Bnz) in three vehicles, saline, peanut oil, or a slow-release vehicle (SRV) and tested for analgesia by both the tail-clip and hotplate techniques. Duration of analgesia as assessed by the tail-clip method was always longer than that by the hotplate when equivalent doses were used in any vehicle. The H.Pam and H.Bnz salts significantly prolonged the analgesia: the mean duration in mice injected with equivalent amounts of heroin base was 3.0 hr for the group receiving heroin HCl in saline and 7.8 hr after H.Bnz in slow-release vehicle. An inverse relationship was evident between the degree of dissociation of H from the three salts, at pH 7.3 and their durations of analgesia in vivo. This was statistically significant (p less than 0.01) at the higher dose level. All mice were challenged with naloxone hydrochloride (1 mg/kg) 24 hr after the injection of each narcotic agonist preparation. The jumping behaviour elicited by naloxone was not consistently related to dose, salt form, or vehicle employed for the injection of agonists, but from 12.5 too 54.2% of all the mice did jump at that time. The durations of analgesia observed and the intensity of the jumping response correlated significantly with the mean number of jumps per mouse after the naloxone challenge.

Analgesia↗

PubMed1977

Variability in development of tolerance to repeated injections of low doses of dl-amphetamine in rats.

Male albino rats received injections of saline for 5 days before and 5 days after a series of 10 daily injections of dl-amphetamine, 1 or 5 mg/kg, sc. Core temperatures were measured every 30 min for 4 h after each injection and feeding activity (on a CRF operant schedule) every 30 min throughout. After amphetamine at either 0800 or 2000 h, a dose-related hyperthermia, stereotypic behavior, and an initial inhibition of feeding occurred. This anorexia decreased over the 4-h post injection period only in the evening-injected rats receiving 5 mg/kg. Mean body weights of all groups continued to increase during amphetamine administration. Mean 24-h food intake tended to remain below that in the control period and the hyperthermic response did not change significantly in any group. Initially on withdrawal from amphetamine all groups showed 'rebound' feeding. Taken with earlier reports, these results suggest that tolerance development to amphetamine-induced anorexia, hyperthermia, and stereotypic behavior occurs at different rates and is dependent upon frequency, route, dose, time, the amphetamine used, and whether the diet was restricted.

Amphetamine↗

PubMed1976

Disruption of diurnal feeding patterns of rats by heroin.

Adult male rats receiving 5 or 20 mg/kg heroin HCl by single injections (08:00 or 20:00 hr) or in 3 equal injections (8 hr intervals) showed a disruption in the normal diurnal pattern of behavior. Initially, heroin abolished feeding for several hr after the injection, reduced the total daily food consumption in a dose-related manner, due primarily to decreased night-time feeding, and prevented or slowed weight gain. Subsequent heroin injections led to a phase of vigorous feeding following the period of depression. Magnitude and duration of the depression decreased, but the stimulatory phase of feeding became more pronounced as tolerance developed. Total daily food intake and body weight returned towards control levels, but the proportion eaten during daylight hr became elevated. Sporadic feeding occurred on the first withdrawal day with abolition of the stimulatory phase which had followed each heroin injection. Subsequently, the normal diurnal pattern of behavior gradually returned. Close measurement of 24 hr food consumption may be a sensitive and valuable measure of the disruptive effects of narcotic analgesics.

Animals↗

PubMed1976

Duration of analgesia in mice after heroin by two testing methods.

The analgestic action in mice of single injections of heroin hydrochloride ranging from 0.3-240mg/kg was measured by the tail-clip and by the hot-plate methods. The duration of analgesia increased as the dose of heroin increased. By the tail-clip technique, the mean effective dose (ED50) (and standard error of estimate) at 30 min was calculated as 1.0 (+/3.42) mg/kg while at 180 min it was 27.5 (+/3.05). By the hot-plate technique the ED50 at 30 min was 4.9 (+/3.13) mg/kg and at 180 min it was 173.8 (+/5.38) mg/kg. The hot-plate method, though less sensitive than the tail-clip method, yields a regression line derived from ED50 values at various testing times of the same slope; thus the two methods give comparable results for changes in analgesia with time. The rate of change of the median analgesic dose of heroin HC1 in mice was calculated to be 2% per minute. In similar mice the acute mean lethal dose for single, subcutaneous injections of heroin HC1 was calculated to be 190.5+/3.01 mg/kg (95% confidence limits).

Analgesia↗

PubMed1976

Changes in diurnal temperature and feeding patterns of rats during repeated injections of heroin and withdrawal.

Rectral temperatures and feeding activity were measured in adult male rats every 30 min for 4 hr, then every 4 hr following daily s.c. injections at 08:00 or 20:00hr or saline or heroin. Initial heroin injections disrupted diurnal temperature and feeding rhythms: 5 mg/kg heroin HCl induced hyperthermia and abolished feeding for 2 hr; 20 mg/kg led to hypothermia, then hyperthermia and abolished feeding for 4 hr. By the 5th heroin day hyperthermia and increased feeding occurred in all groups with a shorter latency to onset. Total food intake was higher than on the 1st heroin day but the diurnal patterns remained disrupted. Changes in both diurnal rhythms again occurred on the 1st withdrawal day as hypothermia, sporadic feeding and hyper-irritability were observed. By the 5th withdrawal day diurnal temperature and feeding rhythms resembled those of the control period. Monitoring diurnal temperature and feeding patterns of rats reveals characteristic dose-related disruptions after heroin which are modified by repeated doses as tolerance develops and which eventually disappear on withdrawal.

Animals↗

PubMed1976

The actions of ketamine on vascular smooth muscle.

The responses of rabbit aortic strips superfused with noradrenaline, adrenaline and 5-HT were studied alone and in combination with ketamine (50 mug/ml). Ketamine caused a slight depression of the isolated aorta but potentiated responses to adrenaline but not to noradrenaline or 5-hydroxytryptamine. Ketamine did not potentiate aortic strips contracted to a stable level by pyrogallol and adrenaline. Experiments carried out with COMT from homogenates of rat liver showed that, in contrast to pyrogallol (10(-5) M), ketamine (10(-3) M) did not inhibit the enzyme. Other experiments with rabbits given 6-hydroxydopamine showed that aortas of these rabbits responded in a similar manner to controls when treated with ketamine and catecholamines. Results obtained with aortas contracted by adrenaline and noradrenaline with ketamine present, followed by oil immersion, showed that ketamine prolonged greatly the relaxation induced by adrenaline and to a lesser extent the relaxation induced by noradrenaline. The results of these studies indicate that ketamine prevented catecholamines from reaching the intracellular site of COMT. In this respect, ketamine can be termed an inhibitor of uptake site 2. If this hypothesis is valid then the action of ketamine on vascular tissue might explain the cardiovascular effects of the drug in man and experimental animals.

Animals↗

PubMed1976

Duration of analgesia and hyperactivity in mice after single injections (S.C. and I.V.) of heroin.

ED50 values for analgesia (tail-clip method) at 30 min after heroin HCl administered i.v. or s.c. in groups of Swiss-Webster mice were not significantly different. Nor was the duration of the analgesia following various doses of heroin significantly different after i.v. or s.c. injections, although there was a tendency for the latter route to have a longer effect. Hyperactivity (mean levels in groups of 5 mice, measured by an Activity Meter), though variable, was increased after s.c. injections of heroin in a dose-related manner up to doses of 10 mg/kg. Larger doses progesssively prolonged the peak levels of hyperactivity. Because the degree and duration of both analgesia and hyperactivity were parallel over a wide range of doses of heroin HCl in these mice, a close relationship between the two underlying mechanisms seems very likely.

Analgesia↗

PubMed1975

Further experimental evidence for a smooth muscle depressant effect of ketamine.

The effect of ketamine on the rat uterus in oestrus and the guinea pig ileum was investigated to determine whether the drug has smooth muscle relaxant properties dependent upon beta adrenergic stimulation or an anticholinergic effect. The results with the rat uterus clearly showed that relaxation was not due to action at the beta adrenergic receptors. On this muscle preparation ketamine depressed carbachol-induced contractions. This anticholinergic action of ketamine was investigated on the guinea pig ileum. Dose response curves were obtained for acetylcholine, histamine and barium chloride in the presence of ketamine. The results showed that ketamine effectively reduced contractions elicited by the three agonists. It is concluded that ketamine is not a beta receptor agonist and it is unlikely that the drug is a specific cholinergic antagonist.

Acetylcholine↗

PubMed1975

Effects of chronic administration of heroin on rats trained on two food reinforcement schedules.

The effects on behaviour and growth of rats given heroin s.c. every 8-hr, and during withdrawal (saline q.8.h.) were studied. Performance of rats trained on one food-reinforcement schedule (FR-10 or VI-10) was tested every day after one of the injections of saline or heroin. Doses of 0.25 mg/kg/injection heroin hydrochloride were increased stepwise to 32 mg/kg as "behavioural tolerance" developed. Threshold doses which blocked feeding in the first 30 min of testing ranged from 0.75 to 4.0 mg/kg and "tolerance" to 32 mg/kg/injection required from 18-71 + days. Heroin interrupted growth in heavier rats; lighter rats gained like saline-treated controls. Within 48 hr of withdrawal bar-pressing increased but all rats lost weight, were hyperirritable, and had diarrhoea. Thereafter, performance and body weight rose steadily. Administration of heroin at regular intervals over a prolonged period, and withdrawal from it, cause a disruption in behaviour comparable to that reported for morphine.

Animals↗

PubMed1974