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Biomedical subjects

A Cowan

Publications and source records attributed to A Cowan.

At least 127 records · Page 7Linked to original sources
PubMed1979

Effects of antipsychotic and antianxiety drugs on the morphine abstinence syndrome in rats.

The effects of representative antipsychotic and antianxiety drugs on the abstinence syndrome in morphine-dependent rats were compared. Groups of 10 to 22 male albino Sprague-Dawley rats (250-300 g) were individually implanted s.c. with either two 75-mg morphine base pellets or two placebo pellets. After 72 hr, chlorpromazine (CPZ 1,2 and 4 mg/kg), haloperidol (0.2, 0.4 and 0.8 mg/kg), thioridazine (10, 20 and 40 mg/kg), chlordiazepoxide (2,4 and 8 mg/kg), diazepam (DPM, 1, 2 and 4 mg/kg) or vehicle was injected s.c. 55 min before precipitation of abstinence with naloxone (1 mg/kg s.c.). Jumping was exacerbated by CPZ (4 mg/kg), chlordiazepoxide (4 and 8 mg/kg) and DPM (1, 2 and 4 mg/kg); haloperidol and thioridazine had no significant effect on this sign. Weight less over 1 hr was decreased by CPZ (4 mg/kg) and DPM (4 mg/kg). Wet-dog shakes were decreased by all doses of haloperidol but increased by chlordiazepoxide (8 mg/kg) and DPM (1, 2 and 4 mg/kg). CPZ (2 and 4 mg/kg) significantly increased the incidence of teeth chattering. Other abstinence signs were not affected in a dose-related manner. Although the antipsychotic agents each decrease dopamine availability at the postsynaptic receptor, this mechanism alone cannot explain their actions on individual signs of abstinence. Perhaps it is therefore time to question how modifying agents can be meaningfully compared in morphine-abstinent rats.

Animals↗
PubMed1978

Lysergic acid diethylamide antagonizes shaking induced in rats by five chemically different compounds.

Thyrotropin-releasing hormone (TRH), sodium valproate, AF-3-5 (1-[2-hydroxyphenyl]-4-[3-nitrophenyl]-1,2,3,6-tetrahydropyrimidine-2-one), RX336-M (7,8-dihydro-5',6'-dimethylcyclohex-5'-eno-1',2',8',14 codeinone), and Sgd 8473 (alpha-[4-chlorobenzylideneamino)-oxy]-isobutyric acid) each induced repetitive shaking of the body of rats after intraperitoneal injection. This action of the five diverse chemicals appears to be subserved by a common pharmacological component, because pretreatment with d-lysergic acid diethylamide (0.03--1.0 mg kg-1, s.c.) attenuated the shaking behavior in a dose-related manner, and cross tolerance was found between RX336-M and TRH, sodium valproate, and AG-3-5.

Animals↗
PubMed1977

Clinical assessment of a new local anesthetic agent-carticaine.

The combination of 4 per cent carticaine 5 mug per milliliter with epinephrine is an effective agent acting in the standard lidocaine-epinephrine-mepivacaine-epinephrine range. Like lidocaine, it is of no clinical value without the addition of epinephrine and its vasodilator properties are greater than those of mepivacaine or prilocaine. Its onset time is reasonably rapid, its duration and extent are satisfactory for clinical purposes, and no toxic reactions were noted in the 100 injections given. However, its predictability for +4 anesthesia is poor, and there is wide variation in the onset time. Finally, the success rate compared with that for lidocaine, mepivacaine, or prilocaine for the same dosage and areas, with the use of the same criteria, is not good enough in my opinion to qualify carticaine as a general-purpose anesthetic on a par with standard lidocaine.

Adolescent↗
PubMed1977

Agonist and antagonist properties of buprenorphine, a new antinociceptive agent.

1. Buprenorphine is a highly lipophilic derivative of oripavine. In rodent antinociceptive assays (writhing, tail pressure), buprenorphine had an action which was rapid in onset and of long duration; it was 25-40 times more potent than morphine after parenteral injection and 7-10 times more potent after oral administration. 2. The log dose-response relationship for buprenorphine was curvilinear in mouse and rat tail flick tests with the antinociceptive effect decreasing at higher, non-toxic doses. 3. Tolerance developed to the antinociceptive activity of buprenorphine in mice. 4. No signs of abstinence were observed on naloxone challenge or after abrupt withdrawal in monkeys receiving buprenorphine chronically for one month. 5. Buprenorphine antagonized the antinociceptive actions of morphine in mouse and rat tail flick tests but was an ineffective antagonist in the rat tail pressure test. 6. Buprenorphine precipitated signs of abstinence in morphine-dependent mice and monkeys but not in morphine-dependent rats. 7. Buprenorphine produced Straub tails in mice. This effect was not antagonized when the animals were pretreated with naloxone. However, in the rat tail pressure test high doses of diprenorphine antagonized established antinociceptive effects of buprenorphine. 8. It is concluded that buprenorphine represents a definite advance in the search for a narcotic antagonist analgesic of low physical dependence potential.

Analgesics↗
PubMed1977

The animal pharmacology of buprenorphine, an oripavine analgesic agent.

1. The general pharmacology of buprenorphine, a potent analgesic agent derived from oripavine, is described. 2. After cute administration of buprenorphine, the spontaneous locomotor activity of mice was increased; rats displayed stereotyped licking and biting movements; behavioural depression was marked in guinea-pigs but mild in rhesus monkeys. The behaviour of cats was unchanged. 3. In general, buprenorphine reduced heart rate but had no significant effect on arterial blood pressure in conscious rats and dogs. 4. In anaesthetized, open-chest cats buprenorphine (0.10 and 1.0 mg/kg, i.v.) caused no major haemodynamic changes. 5. Buprenorphine (0.01-10 mg/kg i.a.) and morphine (0.30-30 mg/kg, i.a.) increased arterial PCO2 values and reduced PO2 values in conscious rats. With doses of buprenorphine greater than 0.10 mg/kg (a) the duration of respiratory depression became less, (b) ceiling effects occurred such that the maximum effects produced were less than those obtained with morphine. 6. Buprenorphine was a potent and long-lasting antagonist of citric acid-induced coughing in guinea-pigs. 7. At a dose level 20 times greater than the ED50 for antinociception (tail pressure), morphine suppressed urine output to a greater extent than the corresponding dose of buprenorphine in rats. 8. Over the range 0.01-1.0 mg/kg (s.c.), buprenorphine slowed the passage of a charcoal meal along the gastrointestinal tract in rats. After doses in excess of 1 mg/kg, the meal travelled increasingly further such that the distances measured at 10 and 30 mg/kg did not differ significantly from control values. In contrast, the morphine dose-response relationship was linear.

Analgesics↗
PubMed1976

Effect of morphine antagonists on drug-induced hypothermia in mice and rats.

Since it has been reported that the narcotic antagonist analgesic, cyclazocine, has thymoleptic activity in man, certain neuropharmacological properties of this compound have been retrospectively analysed in rodents using diprenorphine, naloxone and RX 336-X 336-M (7,8-dihydro-5',6'-dimethylcyclohex-5'-eno 1',2',8',14 codeinone) as reference narcotic antagonists and morphine, desmethylimipramine and d-amphetamine as standard psychotropic agents. From interactional studies with alpha-methylparatyrosine (alpha-MT) in rats, and apomorphine, oxotremorine or reserpine in mice, the calorigenic activities of each compound were compared. Diprenorphine, naloxone and morphine (each at doses ranging from 1-30 mg/kg, s.c.) had no significant calorigenic effect in any test. Evidence of potential antidepressant activity for cyclazocine was based on a high dose (30 mg/kg, s.c.) preventing the development of reserpine-induced hypothermia. RX 336-M (0.5-16 mg/kg, s.c.) reversed established hypothermia in the reserpine and alpha-MT tests. Since this calorigenic action was not antagonised by naloxone it was concluded that narcotic receptors were probably not involved in the mediation of the effect. Although RX 336-M resembled desmethylimipramine and d-amphetamine in the reserpine (reversal) and apomorphine tests, contrasting data from the reserpine (prevention), oxotremorine and alpha-MT tests indicated possible psychotropic activity based on different neurochemical mechanisms.

Animals↗
PubMed1976

Use of the mouse jumping test for estimating antagonistic potencies of morphine antagonists.

The potencies of 19 reference morphine antagonists have been compared in a modified version of the mouse jumping test. Mice were each implanted subcutaneously with one 75 mg pellet of morphine. Antagonist challenge took place 72 h later and the incidence of repetitive vertical-jumping was monitored over 1 h. A high Pearson correlation coefficient (r = 0.997) was found between quantitative assays based on the total number of jumps per mouse and quantal assays based on mice jumping at least 6 times. A comparison of relative potencies obtained with the mouse test and with non-withdrawn morphine-dependent monkeys gave a Spearman rank order coefficient of 0.91 while a similar comparison with values obtained with the guinea-pig isolated ileum preparation also gave a high correlation coefficient (r= 0.92). Whereas it is difficult to assess the antagonistic component of buprenorphine and cyclorphan with the ileum preparation, both compounds can be satisfactorily assayed in the mouse jumping test. The reported antagonistic properties of ketocyclazocine and profadol could not be confirmed in the mouse model.

Animals↗
PubMed1975

Effect of propranolol on antinociceptive, tolerance- and dependence-producing properties of morphine in rodents and monkeys.

Since an abstinence syndrome may accompany the injection of opioids in addicts pretreated with propranolol the morphine antagonistic properties of this compound were investigated. Racemic propranolol did not significantly affect the antinociceptive ED50 of morphine in rodents and neither precipitated abstinence in morphine-dependent monkeys nor exacerbated the syndrome in 24 hr withdrawn monkeys. Multiple doses of propranolol did not alter the development of physical dependence on morphine in monkeys. Clinical narcotic antagonism would not be predicted from this profile. Evidence for a possible propranolol-morphine interaction came from studies using the mouse tail flick test. Thus, after 8 injections of propranolol (over 4 days) mice were tolerant to normally effective doses of morphine. Concurrent injections of naloxone antagonised this effect. When propranolol and morphine were administered concurrently the morphine ED50 (on day 5) was twice that of the group receiving morphine alone. Similar results were obtained with d-propranolol; practolol had a neutral effect.

Analgesics, Opioid↗
PubMed1975

General comments on continuing education.

Dental education should be a continuing process from undergraduate days throughout the dentists' practising life. The development of postgraduate courses has moved earlier the point at which a licence to practise is conferred, and in so doing has increased the responsibility to pursue continuing education and training after licensure. There is a growing tendency for attendance at continuing education courses to become a condition for relicensure in the hope that this will increase the status of the profession and improve the standard of dental care. So long as the requirement is for the attendance at courses this development deserves support. However any suggestion of re-examination should be resisted since this could only lead to increased stress on the competent dentist who was a poor examinee. A questionnaire sent to dental educators produced information on the proportion of dentists currently attending continuing education courses in ten countries and also enabled the popularity of different subjects to be assessed. It is suggested that courses should be arranged so that the whole field of dentistry is covered every five years. If the profession does not organize its own programme of continuing education and motivate its members to participate voluntarily in such courses, governments may well impose upon it requirements which could be less acceptable to the status and dignity of the profession.

Education, Dental, Continuing↗