Robert Capetola - Academia.edu (original) (raw)
Papers by Robert Capetola
The isolation and structural elucidation of LHRH by Schally [1] and Guillemin [2] in 1971 led to ... more The isolation and structural elucidation of LHRH by Schally [1] and Guillemin [2] in 1971 led to the synthesis of analogs which have been proposed for use in a variety of clinical disorders such as endometriosis, precocious puberty and prostatic carcinoma. These analogs have included both agonists, many of which are currently being studied clinically, and more recently, competitive antagonists. The first LHRH antagonists which were synthesized in 1972 [3] were not very potent, but did support the feasibility of synthesizing competitive antagonists. This led to research in many laboratories to improve the potency of antagonists. As reviewed by Karten [4], a large number of chemical modifications of LHRH have been attempted. Substitutions at positions 2, 3 and 6 have been among the most effective, although the structure activity relationships in this work appear to be very complex. One series of analogs with an arginine substituted at position 6 appears to be most potent [5,6]. One of these, [N-Ac-D-Nal(2)1, D-pF-Phe2, D-Trp3, D-Arg6] LHRH has been proposed for clinical studies.
PubMed, Jul 1, 1982
Adjuvant arthritis is an experimental immunopathy that is thought to share many features of human... more Adjuvant arthritis is an experimental immunopathy that is thought to share many features of human rheumatoid arthritis and, as such, is one of the most widely used models for studying the anti-inflammatory properties of compounds. Adjuvant arthritis can be induced in the rat by the injection of various bacterial cell walls or their components; however, the exact immunogen remains unknown. Recently, an autoantibody response to type II collagen was described not only in the collagen-induced arthritic model but in the adjuvant-induced disease as well. This response thus suggests that shared antigenic determinants exist between type II collagen and the responsible immunogen in the bacterial cell wall components. The contribution of the T lymphocyte to the pathogenesis of adjuvant arthritis is well known. It has now been shown that under specific conditions, adjuvant arthritis can be either enhanced or suppressed with pharmacologic or surgical manipulation, thus suggesting the heterogenicity of T lymphocytes capable of influencing the course of the disease. Levamisole was shown to reverse the augmentation of adjuvant disease seen after adult thymectomy, which suggests that levamisole can restore an aberrant immune response. Monoclonal antibodies are now being developed to evaluate T cell subsets in the rat. The use of these antibodies to study or selectively deplete lymphocyte subpopulations in this disease model promises to reveal immunologic characteristics that may lead to the development of new classes of immunoregulant drugs. Finally, the adjuvant rat has been found useful as a pain model capable of detecting the analgesic properties of both central and the newer peripheral analgesics. The above studies further corroborate the similarities between the immunopathological and hyperalgesic features of human rheumatoid arthritis and adjuvant disease. Recently developed immunologic technology may allow a new look at an old model and may result in the ability to evaluate new classes of immunoregulating agents.
Journal of Medicinal Chemistry, Jun 1, 1981
ABSTRACT
Acta dermato-venereologica, Nov 1, 1992
Life Sciences, Jun 1, 1975
ölten thinking of narcotic analgesics, roost pharenacologists are concerned with them only as nar... more ölten thinking of narcotic analgesics, roost pharenacologists are concerned with them only as narcotics or as analgesics. That_, howevßr, is â clinical attitude which disrngarda the many other. actions that opiates also have ; neither their analgesic action nor the developwent of dependence may be beat suited to hAlp understand the interaction of opiates with their receptors.
Cellular Immunology, Apr 1, 1993
Agents and actions, Feb 1, 1987
This survey discusses the correlation between the oral potency of antialgesic drugs in several ph... more This survey discusses the correlation between the oral potency of antialgesic drugs in several pharmacology laboratories and their human oral dose in clinical practice. We also present a brief overview of a few biological assays that have been successfully used to direct the synthesis of newer antialgesic drugs. The laboratory assay that our analysis showed to be most predictive of the clinical analgesic dose is based upon the response of rats to flexion of an arthritic joint. Laboratory ED50 values from the ACh-induced abdominal constriction assay in mice are nearly as predictive while the predictive power of the yeast-induced hyperalgesia assay in rats is somewhat less. Probably because of the small number of experiments, the correlation between the efficacy of these agents in a canine model of synovitis and their clinical doses only reached borderline statistical significance (p = 0.0651). Regression equations are presented that permit calculations of single clinical analgesic doses from efficacy data in individual tests. Calculation of stepwise multiple regression showed that the clinical dose could be best predicted when efficacy data obtained in the joint flexion assay in rats and the ACh-induced constriction assay in mice are both taken into account. We have concluded that the effective doses are highly predictive of clinical efficacy because these animal assays have been designed to reflect the action of drugs upon prostanoid-induced hyperalgesia.
Nucleic Acids Research, 1992
A polymerase chain reaction (PCR) method has been validated for the quantitation of retinoic acid... more A polymerase chain reaction (PCR) method has been validated for the quantitation of retinoic acid (RA) induction of cellular retinoic acid-binding protein 11 (CRABP-11) RNA from cultured human skin fibroblasts and human skin biopsies. The method utilizes reverse transcription and PCR (RT-PCR) to compare cellular CRABP-11 RNA with a known amount of added internal standard RNA generated from a modified CRABP-11 cDNA containing a 42 bp deletion. Thus, after RT-PCR of cellular and standard CRABP-11 RNA in the same tube, the resulting DNA bands could be distinguished by size on ethidium bromide-stained, nondenaturing polyacrylamide gel. Serial dilutions of cellular RNA were co-amplified with a fixed amount of internal standard CRABP-11 RNA, and the ratio of intensities of the two DNA bands was determined by computerized image analysis of the gel photograph. A linear relationship was found between the logs of this ratio and the input RNA. Absolute quantitation of cellular CRABP-11 RNA was determined from the 'equivalence point', the dilution at which band intensities from cellular and standard RNAs were identical. Using this quantitative assay, the amount of CRABP-11 RNA in cultured fibroblasts was 24 attomoles per microgram total RNA. A 4.2-fold increase in CRABP-11 RNA was seen following 24 hours treatment with 10-6 M RA. CRABP-11 RNA content in skin biopsies taken from 3 human subjects ranged from 16 to 25 attomole/IAg RNA. Topical treatment with 0.1% RA cream resulted in induction ranging from 3.9-to 12-fold over vehicle treatment. The method described here offers a rapid, sensitive and quantitative assay of specific RNAs, and should be especially useful for the measurement of RNA levels from small solid-tissue biopsies.
British Journal of Dermatology, Nov 1, 1996
To investigate the effects of long-term all-trans-retinoic acid (RA) treatment on epidermal diffe... more To investigate the effects of long-term all-trans-retinoic acid (RA) treatment on epidermal differentiation in vivo, rhino mice were treated topically with 0.005% RA, and their epidermis was analysed histologically and biochemically after 5, 13 and 26 weeks of treatment. Effects of RA were observed first in the living layers of the epidermis, and then in the non-viable stratum corneum. Five weeks of topical RA led to thickening of the spinous and granular compartments, induction of keratins K6, K16 and K17, and suppression of filaggrin expression. After 13 and 26 weeks of RA treatment, the number of anucleate cornified cell layers remained similar to controls, but additional changes in histology and protein expression were observed. The results showed that prolonged administration of topical RA induced epidermal hyperproliferation, but did not suppress differentiation, in contrast to results observed in keratinocyte cultures. However, the distinct histological and biochemical changes observed in the spinous, granular and cornified layers of RA-treated skin after 26 weeks of treatment, suggested that the progeny of RA-treated basal cells undergo a modified programme of terminal differentiation. Considering the present data together with results of previous in vivo studies, we propose that long-term topical RA treatment retards, or specifically modulates, the later stages in epidermal differentiation, or programmed cell death.
Journal of Cellular Biochemistry, Sep 1, 1992
Glucocorticoids decrease type I procollagen synthesis by decreasing the steady state levels of pr... more Glucocorticoids decrease type I procollagen synthesis by decreasing the steady state levels of procollagen mRNAs and mRNA synthesis. The present studies were undertaken to determine the functional sequences of the proa2(1) collagen gene required for the glucocorticoid-mediated decrease of type I procollagen mRNA synthesis. Embryonic mouse fibroblasts were stably transfected with the pR40 DNA CAT construct containing the 5' flanking region fragment from-2048 to +54 and the intronic fragment from +418 to +1524 of the mouse a2 (I) collagen gene. Dexamethasone treatment of these pR40 transfected fibroblasts resulted in a significant decrease in CAT activity which agrees with the glucocorticoid-mediated decrease of the steady state levels of type I procollagen mRNAs. To determine the possible role of the first intron fragment in the dexamethasone-mediated decrease of CAT activity, pR36, a CAT plasmid containing the first intron fragment and the SV40 early promoter, was transfected into mouse fibroblasts and treated with dexamethasone. No significant decrease in CAT activity was observed. The dexamethasone-mediated response was then localized within the 5' flanking region by preparing a series of constructs containing internal deletions and transfecting these plasmids into mouse fibroblasts. The regions-2048 to-981 and-506 to-351 were required for the dexamethasone response of gene activity. However, the DNA stretch from-981 to-506 was not. Analysis of the DNA sequences of these regions revealed a single GRE at-1023 to-1018 and a modified doublet at-873 to-856. The doublet GRE contains an A/T strand switch of the third base pair as compared to the single GRE and is not necessary for dexamethasone regulation of gene activity. All-trans-retinoic acid increased CAT activity of the same pR40 CAT construct transfected in the mouse fibroblasts. DNA sequencing revealed a RARE and a modified RARE in the stretch of DNA from-981 to-506. Deletion of only the latter DNA region eliminated the elevation of CAT activity elicited by all-trans-retinoic acid. Our results indicate that the singlet CRE and the RARE are required for glucocorticoid and retinoic acid regulation of proa2(I) collagen gene activity, respectively.
Chemischer Informationsdienst, Nov 3, 1981
Elsevier eBooks, 1979
Publisher Summary This chapter summarizes the use of drugs in the treatment of asthma and other a... more Publisher Summary This chapter summarizes the use of drugs in the treatment of asthma and other allergic diseases. Several reviews have examined the role of mediators in the pathophysiology of asthma and other allergic disorders. Numerous pharmacologic agents have been introduced that inhibit the mechanisms responsible for the release of these mediators. Their actions and clinical efficacy have been compared to the prototype drug of this class—that is, disodium cromoglycate (DSCG). Several clinical trials have shown ketotifen to be an effective antiasthmatic compound, and in fact the compound has been marketed in several European countries. In addition to having anti-anaphylactic properties, it is also a potent long acting H receptor antagonist. This chapter also mentions that a series of quinazolinecarboxylic acids have been synthesized and evaluated as potential antiallergic agent. The pharmacology and clinical effectiveness of fenoterol has been recently reviewed with comparisons made to isoproterenol, orciprenaline, and salbutamol. Clinical experience has shown that fenoterol, a highly selective β 2 agonist, is an effective bronchodilator with negligable effects on the cardiovascular system following aerosol administration of usual therapeutic doses. Synthetic prostaglandins similar to PGE continue to be of potential interest in asthma therapy. The sulfur containing analog is reported to be an active bronchodilator but much less potent than PGE. These findings may indicate a modulating role in asthma for these compounds.
International Journal of Immunopharmacology, 1980
Life Sciences, Oct 1, 1987
Studies were conducted with LHRH antagonists examining the relationship of structure to anaphylac... more Studies were conducted with LHRH antagonists examining the relationship of structure to anaphylactoid-like activity and the relationship of anaphylactoid-like activity to anti-ovulatory activity in rats. Substitution of basic amino acids appeared to enhance the anaphylactoid-like activity of these peptides but other complex structural characteristics may also be involved. Anaphylactoid and anti-ovulatory activities were clearly independent and potent LHRH antagonists with minimal anaphylactoid-like activity were identified.
Clinics in rheumatic diseases, Aug 1, 1984
Suprofen is a potent, peripherally-acting, non-narcotic analgesic agent. The mechanism of action ... more Suprofen is a potent, peripherally-acting, non-narcotic analgesic agent. The mechanism of action of the compound involves inhibition of prostaglandin biosynthesis and, perhaps, direct antagonism of the peripheral, pain inducing actions of prostaglandins, bradykinin and other pain mediators. Suprofen at a dose of 200 mg appears to be equal or greater in efficacy as an analgesic modality than those of ibuprofen, propoxyphene, naproxen and diflunisal or a combination of 650 mg aspirin plus 60 mg codeine. Its clinical utility has been amply demonstrated in the treatment of a number of types of pain including general and orthopedic surgery, episiotomy, post-partum pain, dysmenorrhea, dental pain and musculoskeletal disorders. Suprofen represents a new class of orally effective nonnarcotic analgesics with potential for effective clinical use in the treatment of pain.
The Journal of Clinical Pharmacology, Nov 12, 1983
U NTIL the late 1970s, physicians had very little choice in medications for the control of pain. ... more U NTIL the late 1970s, physicians had very little choice in medications for the control of pain. Aspirin and the aniline group of drugs (acetanilid, phenacetin, and acetaminophen) as well as antipyrine, aininopyrine, and related drugs were used for the control of mild pain, and narcotictype analgesics (e.g., morphine, codeine, and meperidine) were used for clinical conditions associated with moderate to severe pain as well as being used as adjunctive drugs in anesthesia. Because of the relatively weak efficacy of compounds such as aspirin and acetaminophen, the major search during the last 75 years has been for a better morphine without harmful side effects.’ Improvements in oral efficacy and duration of action have been obtained, but little progress has been made toward separating the analgesic effects of narcotic-type drugs from their side effects, especially physical dependence and tolerance. The discovery of the mixed agonist-antagonist narcotics revealed for the first time that dependence liability could be minimized from a drug of this type. Unfortunately, new side effects, mainly psychotomimetic in nature, have thus far precluded the widespread use of this group of drugs. A second line of analgesic research involved attempted improvements with the aspirin-like drugs. Although thought to be less promising by many, this approach has led to a new generation of analgesics whose clinical usefulness is only now beginning to be appreciated.
Journal of Medicinal Chemistry, Jun 1, 1981
ABSTRACT
The isolation and structural elucidation of LHRH by Schally [1] and Guillemin [2] in 1971 led to ... more The isolation and structural elucidation of LHRH by Schally [1] and Guillemin [2] in 1971 led to the synthesis of analogs which have been proposed for use in a variety of clinical disorders such as endometriosis, precocious puberty and prostatic carcinoma. These analogs have included both agonists, many of which are currently being studied clinically, and more recently, competitive antagonists. The first LHRH antagonists which were synthesized in 1972 [3] were not very potent, but did support the feasibility of synthesizing competitive antagonists. This led to research in many laboratories to improve the potency of antagonists. As reviewed by Karten [4], a large number of chemical modifications of LHRH have been attempted. Substitutions at positions 2, 3 and 6 have been among the most effective, although the structure activity relationships in this work appear to be very complex. One series of analogs with an arginine substituted at position 6 appears to be most potent [5,6]. One of these, [N-Ac-D-Nal(2)1, D-pF-Phe2, D-Trp3, D-Arg6] LHRH has been proposed for clinical studies.
PubMed, Jul 1, 1982
Adjuvant arthritis is an experimental immunopathy that is thought to share many features of human... more Adjuvant arthritis is an experimental immunopathy that is thought to share many features of human rheumatoid arthritis and, as such, is one of the most widely used models for studying the anti-inflammatory properties of compounds. Adjuvant arthritis can be induced in the rat by the injection of various bacterial cell walls or their components; however, the exact immunogen remains unknown. Recently, an autoantibody response to type II collagen was described not only in the collagen-induced arthritic model but in the adjuvant-induced disease as well. This response thus suggests that shared antigenic determinants exist between type II collagen and the responsible immunogen in the bacterial cell wall components. The contribution of the T lymphocyte to the pathogenesis of adjuvant arthritis is well known. It has now been shown that under specific conditions, adjuvant arthritis can be either enhanced or suppressed with pharmacologic or surgical manipulation, thus suggesting the heterogenicity of T lymphocytes capable of influencing the course of the disease. Levamisole was shown to reverse the augmentation of adjuvant disease seen after adult thymectomy, which suggests that levamisole can restore an aberrant immune response. Monoclonal antibodies are now being developed to evaluate T cell subsets in the rat. The use of these antibodies to study or selectively deplete lymphocyte subpopulations in this disease model promises to reveal immunologic characteristics that may lead to the development of new classes of immunoregulant drugs. Finally, the adjuvant rat has been found useful as a pain model capable of detecting the analgesic properties of both central and the newer peripheral analgesics. The above studies further corroborate the similarities between the immunopathological and hyperalgesic features of human rheumatoid arthritis and adjuvant disease. Recently developed immunologic technology may allow a new look at an old model and may result in the ability to evaluate new classes of immunoregulating agents.
Journal of Medicinal Chemistry, Jun 1, 1981
ABSTRACT
Acta dermato-venereologica, Nov 1, 1992
Life Sciences, Jun 1, 1975
ölten thinking of narcotic analgesics, roost pharenacologists are concerned with them only as nar... more ölten thinking of narcotic analgesics, roost pharenacologists are concerned with them only as narcotics or as analgesics. That_, howevßr, is â clinical attitude which disrngarda the many other. actions that opiates also have ; neither their analgesic action nor the developwent of dependence may be beat suited to hAlp understand the interaction of opiates with their receptors.
Cellular Immunology, Apr 1, 1993
Agents and actions, Feb 1, 1987
This survey discusses the correlation between the oral potency of antialgesic drugs in several ph... more This survey discusses the correlation between the oral potency of antialgesic drugs in several pharmacology laboratories and their human oral dose in clinical practice. We also present a brief overview of a few biological assays that have been successfully used to direct the synthesis of newer antialgesic drugs. The laboratory assay that our analysis showed to be most predictive of the clinical analgesic dose is based upon the response of rats to flexion of an arthritic joint. Laboratory ED50 values from the ACh-induced abdominal constriction assay in mice are nearly as predictive while the predictive power of the yeast-induced hyperalgesia assay in rats is somewhat less. Probably because of the small number of experiments, the correlation between the efficacy of these agents in a canine model of synovitis and their clinical doses only reached borderline statistical significance (p = 0.0651). Regression equations are presented that permit calculations of single clinical analgesic doses from efficacy data in individual tests. Calculation of stepwise multiple regression showed that the clinical dose could be best predicted when efficacy data obtained in the joint flexion assay in rats and the ACh-induced constriction assay in mice are both taken into account. We have concluded that the effective doses are highly predictive of clinical efficacy because these animal assays have been designed to reflect the action of drugs upon prostanoid-induced hyperalgesia.
Nucleic Acids Research, 1992
A polymerase chain reaction (PCR) method has been validated for the quantitation of retinoic acid... more A polymerase chain reaction (PCR) method has been validated for the quantitation of retinoic acid (RA) induction of cellular retinoic acid-binding protein 11 (CRABP-11) RNA from cultured human skin fibroblasts and human skin biopsies. The method utilizes reverse transcription and PCR (RT-PCR) to compare cellular CRABP-11 RNA with a known amount of added internal standard RNA generated from a modified CRABP-11 cDNA containing a 42 bp deletion. Thus, after RT-PCR of cellular and standard CRABP-11 RNA in the same tube, the resulting DNA bands could be distinguished by size on ethidium bromide-stained, nondenaturing polyacrylamide gel. Serial dilutions of cellular RNA were co-amplified with a fixed amount of internal standard CRABP-11 RNA, and the ratio of intensities of the two DNA bands was determined by computerized image analysis of the gel photograph. A linear relationship was found between the logs of this ratio and the input RNA. Absolute quantitation of cellular CRABP-11 RNA was determined from the 'equivalence point', the dilution at which band intensities from cellular and standard RNAs were identical. Using this quantitative assay, the amount of CRABP-11 RNA in cultured fibroblasts was 24 attomoles per microgram total RNA. A 4.2-fold increase in CRABP-11 RNA was seen following 24 hours treatment with 10-6 M RA. CRABP-11 RNA content in skin biopsies taken from 3 human subjects ranged from 16 to 25 attomole/IAg RNA. Topical treatment with 0.1% RA cream resulted in induction ranging from 3.9-to 12-fold over vehicle treatment. The method described here offers a rapid, sensitive and quantitative assay of specific RNAs, and should be especially useful for the measurement of RNA levels from small solid-tissue biopsies.
British Journal of Dermatology, Nov 1, 1996
To investigate the effects of long-term all-trans-retinoic acid (RA) treatment on epidermal diffe... more To investigate the effects of long-term all-trans-retinoic acid (RA) treatment on epidermal differentiation in vivo, rhino mice were treated topically with 0.005% RA, and their epidermis was analysed histologically and biochemically after 5, 13 and 26 weeks of treatment. Effects of RA were observed first in the living layers of the epidermis, and then in the non-viable stratum corneum. Five weeks of topical RA led to thickening of the spinous and granular compartments, induction of keratins K6, K16 and K17, and suppression of filaggrin expression. After 13 and 26 weeks of RA treatment, the number of anucleate cornified cell layers remained similar to controls, but additional changes in histology and protein expression were observed. The results showed that prolonged administration of topical RA induced epidermal hyperproliferation, but did not suppress differentiation, in contrast to results observed in keratinocyte cultures. However, the distinct histological and biochemical changes observed in the spinous, granular and cornified layers of RA-treated skin after 26 weeks of treatment, suggested that the progeny of RA-treated basal cells undergo a modified programme of terminal differentiation. Considering the present data together with results of previous in vivo studies, we propose that long-term topical RA treatment retards, or specifically modulates, the later stages in epidermal differentiation, or programmed cell death.
Journal of Cellular Biochemistry, Sep 1, 1992
Glucocorticoids decrease type I procollagen synthesis by decreasing the steady state levels of pr... more Glucocorticoids decrease type I procollagen synthesis by decreasing the steady state levels of procollagen mRNAs and mRNA synthesis. The present studies were undertaken to determine the functional sequences of the proa2(1) collagen gene required for the glucocorticoid-mediated decrease of type I procollagen mRNA synthesis. Embryonic mouse fibroblasts were stably transfected with the pR40 DNA CAT construct containing the 5' flanking region fragment from-2048 to +54 and the intronic fragment from +418 to +1524 of the mouse a2 (I) collagen gene. Dexamethasone treatment of these pR40 transfected fibroblasts resulted in a significant decrease in CAT activity which agrees with the glucocorticoid-mediated decrease of the steady state levels of type I procollagen mRNAs. To determine the possible role of the first intron fragment in the dexamethasone-mediated decrease of CAT activity, pR36, a CAT plasmid containing the first intron fragment and the SV40 early promoter, was transfected into mouse fibroblasts and treated with dexamethasone. No significant decrease in CAT activity was observed. The dexamethasone-mediated response was then localized within the 5' flanking region by preparing a series of constructs containing internal deletions and transfecting these plasmids into mouse fibroblasts. The regions-2048 to-981 and-506 to-351 were required for the dexamethasone response of gene activity. However, the DNA stretch from-981 to-506 was not. Analysis of the DNA sequences of these regions revealed a single GRE at-1023 to-1018 and a modified doublet at-873 to-856. The doublet GRE contains an A/T strand switch of the third base pair as compared to the single GRE and is not necessary for dexamethasone regulation of gene activity. All-trans-retinoic acid increased CAT activity of the same pR40 CAT construct transfected in the mouse fibroblasts. DNA sequencing revealed a RARE and a modified RARE in the stretch of DNA from-981 to-506. Deletion of only the latter DNA region eliminated the elevation of CAT activity elicited by all-trans-retinoic acid. Our results indicate that the singlet CRE and the RARE are required for glucocorticoid and retinoic acid regulation of proa2(I) collagen gene activity, respectively.
Chemischer Informationsdienst, Nov 3, 1981
Elsevier eBooks, 1979
Publisher Summary This chapter summarizes the use of drugs in the treatment of asthma and other a... more Publisher Summary This chapter summarizes the use of drugs in the treatment of asthma and other allergic diseases. Several reviews have examined the role of mediators in the pathophysiology of asthma and other allergic disorders. Numerous pharmacologic agents have been introduced that inhibit the mechanisms responsible for the release of these mediators. Their actions and clinical efficacy have been compared to the prototype drug of this class—that is, disodium cromoglycate (DSCG). Several clinical trials have shown ketotifen to be an effective antiasthmatic compound, and in fact the compound has been marketed in several European countries. In addition to having anti-anaphylactic properties, it is also a potent long acting H receptor antagonist. This chapter also mentions that a series of quinazolinecarboxylic acids have been synthesized and evaluated as potential antiallergic agent. The pharmacology and clinical effectiveness of fenoterol has been recently reviewed with comparisons made to isoproterenol, orciprenaline, and salbutamol. Clinical experience has shown that fenoterol, a highly selective β 2 agonist, is an effective bronchodilator with negligable effects on the cardiovascular system following aerosol administration of usual therapeutic doses. Synthetic prostaglandins similar to PGE continue to be of potential interest in asthma therapy. The sulfur containing analog is reported to be an active bronchodilator but much less potent than PGE. These findings may indicate a modulating role in asthma for these compounds.
International Journal of Immunopharmacology, 1980
Life Sciences, Oct 1, 1987
Studies were conducted with LHRH antagonists examining the relationship of structure to anaphylac... more Studies were conducted with LHRH antagonists examining the relationship of structure to anaphylactoid-like activity and the relationship of anaphylactoid-like activity to anti-ovulatory activity in rats. Substitution of basic amino acids appeared to enhance the anaphylactoid-like activity of these peptides but other complex structural characteristics may also be involved. Anaphylactoid and anti-ovulatory activities were clearly independent and potent LHRH antagonists with minimal anaphylactoid-like activity were identified.
Clinics in rheumatic diseases, Aug 1, 1984
Suprofen is a potent, peripherally-acting, non-narcotic analgesic agent. The mechanism of action ... more Suprofen is a potent, peripherally-acting, non-narcotic analgesic agent. The mechanism of action of the compound involves inhibition of prostaglandin biosynthesis and, perhaps, direct antagonism of the peripheral, pain inducing actions of prostaglandins, bradykinin and other pain mediators. Suprofen at a dose of 200 mg appears to be equal or greater in efficacy as an analgesic modality than those of ibuprofen, propoxyphene, naproxen and diflunisal or a combination of 650 mg aspirin plus 60 mg codeine. Its clinical utility has been amply demonstrated in the treatment of a number of types of pain including general and orthopedic surgery, episiotomy, post-partum pain, dysmenorrhea, dental pain and musculoskeletal disorders. Suprofen represents a new class of orally effective nonnarcotic analgesics with potential for effective clinical use in the treatment of pain.
The Journal of Clinical Pharmacology, Nov 12, 1983
U NTIL the late 1970s, physicians had very little choice in medications for the control of pain. ... more U NTIL the late 1970s, physicians had very little choice in medications for the control of pain. Aspirin and the aniline group of drugs (acetanilid, phenacetin, and acetaminophen) as well as antipyrine, aininopyrine, and related drugs were used for the control of mild pain, and narcotictype analgesics (e.g., morphine, codeine, and meperidine) were used for clinical conditions associated with moderate to severe pain as well as being used as adjunctive drugs in anesthesia. Because of the relatively weak efficacy of compounds such as aspirin and acetaminophen, the major search during the last 75 years has been for a better morphine without harmful side effects.’ Improvements in oral efficacy and duration of action have been obtained, but little progress has been made toward separating the analgesic effects of narcotic-type drugs from their side effects, especially physical dependence and tolerance. The discovery of the mixed agonist-antagonist narcotics revealed for the first time that dependence liability could be minimized from a drug of this type. Unfortunately, new side effects, mainly psychotomimetic in nature, have thus far precluded the widespread use of this group of drugs. A second line of analgesic research involved attempted improvements with the aspirin-like drugs. Although thought to be less promising by many, this approach has led to a new generation of analgesics whose clinical usefulness is only now beginning to be appreciated.
Journal of Medicinal Chemistry, Jun 1, 1981
ABSTRACT