The study of the potentiation of anticholinergic side effects of tricyclic antidepressives by female sex steroids
- Authors: Kok, Eric Charl
- Date: 1981
- Subjects: Antidepressants , Steroid hormones
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3822 , http://hdl.handle.net/10962/d1005623 , Antidepressants , Steroid hormones
- Description: It has been recorded that women respond to tricyclic antidepressives with a greater incidence of anticholinergic side effects than men do, particularly women taking an exogenous source of oestrogen. The aim of this study was to investigate the influence that ethinyl oestradiol and Premarin© had on the metabolism of a number of tricyclic antidepressives, and also the influence they had on the binding ability of microsomes to imipramine. Rat hepatocyctes and microsomes were used. Detection techniques used were High Pressure Liquid Chromatography and Spectrophotometry respectively. In addition to these studies, a study of the anticholinergic activity of Nomifensine, tricyclic antidepressives and their derivatives was performed on a rat jujenum. Results conclusively showed that ethinyl oestradiol had a marked influence on the metabolism of the tricyclic antidepressives studied. Premarin© had Iittle, if any influence. However, both ethinyl oestradiol and Premarin© affected the binding of microsomes to imipramine, but ethinyl oestradiol had the greater effect. The parent compound in each case exhibited a higher pAZ value. Results indicate that a possible explanation for the increased anticholinergic side effect is due to an inhibition of the metabolism of the tricyclic antidepressives by oestrogen.
- Full Text:
- Date Issued: 1981
- Authors: Kok, Eric Charl
- Date: 1981
- Subjects: Antidepressants , Steroid hormones
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3822 , http://hdl.handle.net/10962/d1005623 , Antidepressants , Steroid hormones
- Description: It has been recorded that women respond to tricyclic antidepressives with a greater incidence of anticholinergic side effects than men do, particularly women taking an exogenous source of oestrogen. The aim of this study was to investigate the influence that ethinyl oestradiol and Premarin© had on the metabolism of a number of tricyclic antidepressives, and also the influence they had on the binding ability of microsomes to imipramine. Rat hepatocyctes and microsomes were used. Detection techniques used were High Pressure Liquid Chromatography and Spectrophotometry respectively. In addition to these studies, a study of the anticholinergic activity of Nomifensine, tricyclic antidepressives and their derivatives was performed on a rat jujenum. Results conclusively showed that ethinyl oestradiol had a marked influence on the metabolism of the tricyclic antidepressives studied. Premarin© had Iittle, if any influence. However, both ethinyl oestradiol and Premarin© affected the binding of microsomes to imipramine, but ethinyl oestradiol had the greater effect. The parent compound in each case exhibited a higher pAZ value. Results indicate that a possible explanation for the increased anticholinergic side effect is due to an inhibition of the metabolism of the tricyclic antidepressives by oestrogen.
- Full Text:
- Date Issued: 1981
The evaluation of melatonin as a possible antidepressive
- Authors: Skene, Debra Jean
- Date: 1980
- Subjects: Melatonin , Antidepressants
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3728 , http://hdl.handle.net/10962/d1001465
- Description: Melatonin, a hormone of the pineal gland, was evaluated in a variety of animal models of depression. Measurements of the frog righting reflex and rat locomotor activity showed that low doses of melatonin have a serotonin-like potentiating effect following monoamine oxidase inhibition. High doses of melatonin caused a reduction in the duration of rat immobility in the Porsolt model of depression and exerted a chlorpromazine-like effect on conditioned avoidance behaviour. In view of the indoleamine hypothesis of depressive disorders, the possibility of melatonin being a potential antidepressive is discussed and it is concluded that melatonin might be useful in the treatment of "agitated" depressions
- Full Text:
- Date Issued: 1980
- Authors: Skene, Debra Jean
- Date: 1980
- Subjects: Melatonin , Antidepressants
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3728 , http://hdl.handle.net/10962/d1001465
- Description: Melatonin, a hormone of the pineal gland, was evaluated in a variety of animal models of depression. Measurements of the frog righting reflex and rat locomotor activity showed that low doses of melatonin have a serotonin-like potentiating effect following monoamine oxidase inhibition. High doses of melatonin caused a reduction in the duration of rat immobility in the Porsolt model of depression and exerted a chlorpromazine-like effect on conditioned avoidance behaviour. In view of the indoleamine hypothesis of depressive disorders, the possibility of melatonin being a potential antidepressive is discussed and it is concluded that melatonin might be useful in the treatment of "agitated" depressions
- Full Text:
- Date Issued: 1980
Adreno-active substances and the pineal gland
- Authors: Midlane, Graham Wallace
- Date: 1979
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3738 , http://hdl.handle.net/10962/d1001530
- Description: The pineal gland, a biochemically very active neuroendocrine transducer which is innervated by the sympathetic nervous system, was used in vivo to evaluate the effect of different þ-adrenoceptor agonists and antagonists on pineal enzyme levels. Hydroxyindole-O-methyltransferase (HIOMT), an enzyme with a circadian activity and unknown control was not significantly affected by these drugs. The activity of serotonin N-acetyltransferase, another pineal enzyme with a greater amplitude of circadian rhythmicity and which is under noradrenergic neural control, the degree of blockade depending on the selectivity and affinity of the agent used. An attempt was also made to alter the oestrous cycle of the rat by dosing with þ-active substances. Only propranolol had any effect on the oestrous cycle. It was not possible to establish an absolute link between the alteration in pineal enzyme activity and an influence on the oestrous cycle. It was concluded that the pineal enzyme studies are useful pharmacological means for evaluating þ-active substances
- Full Text:
- Date Issued: 1979
- Authors: Midlane, Graham Wallace
- Date: 1979
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3738 , http://hdl.handle.net/10962/d1001530
- Description: The pineal gland, a biochemically very active neuroendocrine transducer which is innervated by the sympathetic nervous system, was used in vivo to evaluate the effect of different þ-adrenoceptor agonists and antagonists on pineal enzyme levels. Hydroxyindole-O-methyltransferase (HIOMT), an enzyme with a circadian activity and unknown control was not significantly affected by these drugs. The activity of serotonin N-acetyltransferase, another pineal enzyme with a greater amplitude of circadian rhythmicity and which is under noradrenergic neural control, the degree of blockade depending on the selectivity and affinity of the agent used. An attempt was also made to alter the oestrous cycle of the rat by dosing with þ-active substances. Only propranolol had any effect on the oestrous cycle. It was not possible to establish an absolute link between the alteration in pineal enzyme activity and an influence on the oestrous cycle. It was concluded that the pineal enzyme studies are useful pharmacological means for evaluating þ-active substances
- Full Text:
- Date Issued: 1979
Aspects of the bioavailability of topical corticosteroid formulations
- Authors: Magnus, Ashley Denis
- Date: 1979
- Subjects: Adrenocortical hormones , Dermatopharmacology , Dermatologic agents , Transdermal medication
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3724 , http://hdl.handle.net/10962/d1001458
- Description: Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17- valerate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base caused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained from the systematic studies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society
- Full Text:
- Date Issued: 1979
- Authors: Magnus, Ashley Denis
- Date: 1979
- Subjects: Adrenocortical hormones , Dermatopharmacology , Dermatologic agents , Transdermal medication
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3724 , http://hdl.handle.net/10962/d1001458
- Description: Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17- valerate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base caused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained from the systematic studies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society
- Full Text:
- Date Issued: 1979
The in vivo and quantitative assessment of topical corticosteroid formulations
- Authors: Coleman, Gerald Leslie
- Date: 1978 , 2013-10-14
- Subjects: Dermatopharmacology , Dermatologic agents , Skin absorption , Adrenocortical hormones -- Therapeutic use , Transdermal medication -- Evaluation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3857 , http://hdl.handle.net/10962/d1013337
- Full Text:
- Date Issued: 1978
- Authors: Coleman, Gerald Leslie
- Date: 1978 , 2013-10-14
- Subjects: Dermatopharmacology , Dermatologic agents , Skin absorption , Adrenocortical hormones -- Therapeutic use , Transdermal medication -- Evaluation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3857 , http://hdl.handle.net/10962/d1013337
- Full Text:
- Date Issued: 1978
The study of the metabolism of phenylbutazone (4-butyl-1,2 -diphenylpyrazolidine - 3,5 - dione) in rats
- Authors: Alexander, Dorothy Mary
- Date: 1978 , 2013-10-18
- Subjects: Drugs -- Metabolism , Phenylbutazone
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3832 , http://hdl.handle.net/10962/d1007468 , Drugs -- Metabolism , Phenylbutazone
- Description: In this study the metabolism of the anti-arthritic drug, phenylbutazone, was investigated in female Wistar rats, and the results compared with those of other workers in this field. Two interrelated projects were undertaken. The first covered the pattern of excretion, isolation and characterisation of the metabolites and decomposition products of phenylbutazone in rats dosed post-orally with the drug. It was found that the major route of excretion was via the urine and over 50% of the administered dose was excreted in the first 24 hours by this route. A small percentage of the dose was excreted in the faeces. The following compounds were identified using chromatographic and autoradiographic techniques: p-Hydroxy derivative of phenylbutazone γ-Hydroxy derivative of phenylbutazone in both its molecular forms (ring lactone and straight chain hydroxyl) 4-Hydroxy derivative of phenylbutazone p-γ-Dihydroxy derivative of phenylbutazone p-4-Dihydroxy derivative of phenylbutazone Hydrolysable conjugates (possibly glucuronides) Water soluble non-hydrolysable conjugates. The second project dealt with the quantitation of the water insoluble compounds isolated in the initial work. Using a unique technique, combining inverse isotope dilution assay and spectrophotometric analysis, it was found that the major metabolite was the γ-hydroxy derivative of phenylbutazone, present in both its molecular forms. Oxyphenbutazone was a minor metabolite and the p-γ-dihydroxy derivative of phenylbutazone was present only in very low concentration. These results did not conform with those of previous workers in this field who reported the γ-hydroxy derivative of phenylbutazone, in one molecular form only, as the major metabolite and the dihydroxy derivative as the second metabolite with a higher concentration in the urine than oxyphenbutazone. This disparity could be due to the fact that these workers took no account of the presence of the two molecular forms of the γ-hydroxy derivative of phenylbutazone with their different polarities and different Rf values. The present study showed that the straight chain hydroxyl isomer was probably mistakenly identified as the p-γ-dihydroxy derivative of phenylbutazone. This theory is supported by the fact that the percentage dose recovered by the previous workers of the γ-hydroxy and p-γ-dihydroxy derivatives together equalled the percentage dose recovered in this study of the two molecular forms of the γ-hydroxy derivative. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Date Issued: 1978
- Authors: Alexander, Dorothy Mary
- Date: 1978 , 2013-10-18
- Subjects: Drugs -- Metabolism , Phenylbutazone
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3832 , http://hdl.handle.net/10962/d1007468 , Drugs -- Metabolism , Phenylbutazone
- Description: In this study the metabolism of the anti-arthritic drug, phenylbutazone, was investigated in female Wistar rats, and the results compared with those of other workers in this field. Two interrelated projects were undertaken. The first covered the pattern of excretion, isolation and characterisation of the metabolites and decomposition products of phenylbutazone in rats dosed post-orally with the drug. It was found that the major route of excretion was via the urine and over 50% of the administered dose was excreted in the first 24 hours by this route. A small percentage of the dose was excreted in the faeces. The following compounds were identified using chromatographic and autoradiographic techniques: p-Hydroxy derivative of phenylbutazone γ-Hydroxy derivative of phenylbutazone in both its molecular forms (ring lactone and straight chain hydroxyl) 4-Hydroxy derivative of phenylbutazone p-γ-Dihydroxy derivative of phenylbutazone p-4-Dihydroxy derivative of phenylbutazone Hydrolysable conjugates (possibly glucuronides) Water soluble non-hydrolysable conjugates. The second project dealt with the quantitation of the water insoluble compounds isolated in the initial work. Using a unique technique, combining inverse isotope dilution assay and spectrophotometric analysis, it was found that the major metabolite was the γ-hydroxy derivative of phenylbutazone, present in both its molecular forms. Oxyphenbutazone was a minor metabolite and the p-γ-dihydroxy derivative of phenylbutazone was present only in very low concentration. These results did not conform with those of previous workers in this field who reported the γ-hydroxy derivative of phenylbutazone, in one molecular form only, as the major metabolite and the dihydroxy derivative as the second metabolite with a higher concentration in the urine than oxyphenbutazone. This disparity could be due to the fact that these workers took no account of the presence of the two molecular forms of the γ-hydroxy derivative of phenylbutazone with their different polarities and different Rf values. The present study showed that the straight chain hydroxyl isomer was probably mistakenly identified as the p-γ-dihydroxy derivative of phenylbutazone. This theory is supported by the fact that the percentage dose recovered by the previous workers of the γ-hydroxy and p-γ-dihydroxy derivatives together equalled the percentage dose recovered in this study of the two molecular forms of the γ-hydroxy derivative. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Date Issued: 1978
A study of the rabbit eye test system to determine the activity of acidic non-steroidal anti-inflammatory agents
- Authors: Wiseman, Ian Charles
- Date: 1977
- Subjects: Nonsteroidal anti-inflammatory agents , Anti-inflammatory agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3855 , http://hdl.handle.net/10962/d1013276
- Description: From introduction : "Inflammation per se, has been defined sufficiently to permit a rational approach to the search for drugs that modify this process, but satisfactory animal models for most rheumatoid diseases are not available". (Swingle 1974) In the search for new meaningful procedures for the detection and evaluation of anti-inflammatory drugs, the rabbit eye as a test system was studied.
- Full Text:
- Date Issued: 1977
- Authors: Wiseman, Ian Charles
- Date: 1977
- Subjects: Nonsteroidal anti-inflammatory agents , Anti-inflammatory agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3855 , http://hdl.handle.net/10962/d1013276
- Description: From introduction : "Inflammation per se, has been defined sufficiently to permit a rational approach to the search for drugs that modify this process, but satisfactory animal models for most rheumatoid diseases are not available". (Swingle 1974) In the search for new meaningful procedures for the detection and evaluation of anti-inflammatory drugs, the rabbit eye as a test system was studied.
- Full Text:
- Date Issued: 1977
A gas chromatographic study of oils from some Agathosma species (family Rutaceae)
- Persicaner, Peter Henry Robert
- Authors: Persicaner, Peter Henry Robert
- Date: 1972 , 2013-11-13
- Subjects: Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3837 , http://hdl.handle.net/10962/d1007634 , Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Description: From Introduction: Buchu leaf is a very widely used household medicine in South Africa, and is usually administered in the form of a brandy tincture or a vinegar, known as "buchu brandy" and "buchu vinegar" respectively. These preparations have a great reputation in curing diseases of the kidney and urinary tract, and in addition are employed as local applications to bruises, and for the relief of rheumatic pains. We owe its introduction into medicine to the Hottentot, who gave the name "buchu" or "bookoo" to any aromatic herb or shrub which they found suitable for use as a dusting powder.
- Full Text:
- Date Issued: 1972
- Authors: Persicaner, Peter Henry Robert
- Date: 1972 , 2013-11-13
- Subjects: Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3837 , http://hdl.handle.net/10962/d1007634 , Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Description: From Introduction: Buchu leaf is a very widely used household medicine in South Africa, and is usually administered in the form of a brandy tincture or a vinegar, known as "buchu brandy" and "buchu vinegar" respectively. These preparations have a great reputation in curing diseases of the kidney and urinary tract, and in addition are employed as local applications to bruises, and for the relief of rheumatic pains. We owe its introduction into medicine to the Hottentot, who gave the name "buchu" or "bookoo" to any aromatic herb or shrub which they found suitable for use as a dusting powder.
- Full Text:
- Date Issued: 1972
An investigation into chemical and biological assays of new compounds from aloes
- Authors: Mapp, R K
- Date: 1969
- Subjects: Medicinal plants -- Research -- South Africa , Botanical chemistry , Aloe -- Analysis , Aloe -- Research -- South Africa , Aloe , Aloin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3850 , http://hdl.handle.net/10962/d1012830
- Description: The drug aloes has been known since earliest times and is mentioned in the Ebers papyrus of circa 1,500 B.C. Alexander the Great is reported to have sent a commission to Socotra to investigate the aloes grown there. The chemical composition of aloes is complex, and being of plant origin, subject to variation. Both the complexity of the chemical constituents and their biological variation has resulted in a very large volume of conflicting material being published on this drug export. Since aloes is used as a purgative for both human and veterinary use, it is obviously important that the dosage and consequently the active constituents, should comply to an accurate means of standardisation. To date, despite extensive world wide research into this drug such standardisation has not been achieved. Even the methods used for the assay of the principal constituent, aloin, vary considerably in their results, and to complicate matters new chemical principles have been isolated from aloes in recent years. Consequently the purpose of this work has been to investigate the main chemical assay methods currently in use, and to determine which was the most accurate, and why discrepancies occurred in the selected assay methods. furthermore the results obtained by chemical assay have been compared with those obtained by biological assay in an attempt to correlate aloin content with purgative activity. Newly isolated compounds have been investigated biologically for the first time, and the biological assays of the resinous, glycosidal and other compounds of aloes have been performed. Intro. p.1-2.
- Full Text:
- Date Issued: 1969
- Authors: Mapp, R K
- Date: 1969
- Subjects: Medicinal plants -- Research -- South Africa , Botanical chemistry , Aloe -- Analysis , Aloe -- Research -- South Africa , Aloe , Aloin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3850 , http://hdl.handle.net/10962/d1012830
- Description: The drug aloes has been known since earliest times and is mentioned in the Ebers papyrus of circa 1,500 B.C. Alexander the Great is reported to have sent a commission to Socotra to investigate the aloes grown there. The chemical composition of aloes is complex, and being of plant origin, subject to variation. Both the complexity of the chemical constituents and their biological variation has resulted in a very large volume of conflicting material being published on this drug export. Since aloes is used as a purgative for both human and veterinary use, it is obviously important that the dosage and consequently the active constituents, should comply to an accurate means of standardisation. To date, despite extensive world wide research into this drug such standardisation has not been achieved. Even the methods used for the assay of the principal constituent, aloin, vary considerably in their results, and to complicate matters new chemical principles have been isolated from aloes in recent years. Consequently the purpose of this work has been to investigate the main chemical assay methods currently in use, and to determine which was the most accurate, and why discrepancies occurred in the selected assay methods. furthermore the results obtained by chemical assay have been compared with those obtained by biological assay in an attempt to correlate aloin content with purgative activity. Newly isolated compounds have been investigated biologically for the first time, and the biological assays of the resinous, glycosidal and other compounds of aloes have been performed. Intro. p.1-2.
- Full Text:
- Date Issued: 1969
An investigation of chlorbutol in ophthalmic and parenteral solutions
- Authors: Summers, Robert Stanley
- Date: 1967
- Subjects: Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3842 , http://hdl.handle.net/10962/d1007694 , Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Description: From Introduction Chlorbutol , which is tri-chlor-tertiary-butanol, was first prepared by Willgerodt in 1886 (1). The reaction he used for its preparation is still used today, though slightly modified (2)(3)(4), and is suggested by its original name "acetone-chloroform". The substance was prepared by adding solid potassium hydroxide to a cold mixture of acetone and chloroform (5 ). Chlorbutol is a derivative of the trichlorinated derivative of methane, and its formation may best be described by the use of structural formulae.
- Full Text:
- Date Issued: 1967
- Authors: Summers, Robert Stanley
- Date: 1967
- Subjects: Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3842 , http://hdl.handle.net/10962/d1007694 , Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Description: From Introduction Chlorbutol , which is tri-chlor-tertiary-butanol, was first prepared by Willgerodt in 1886 (1). The reaction he used for its preparation is still used today, though slightly modified (2)(3)(4), and is suggested by its original name "acetone-chloroform". The substance was prepared by adding solid potassium hydroxide to a cold mixture of acetone and chloroform (5 ). Chlorbutol is a derivative of the trichlorinated derivative of methane, and its formation may best be described by the use of structural formulae.
- Full Text:
- Date Issued: 1967