I= EVALUATION OF RECEPTOR ACTIVITY OF NEWLY SYNTHESIZED PIPERIDINE DERIVATES
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Title of Thesis
EVALUATION OF RECEPTOR ACTIVITY OF NEWLY SYNTHESIZED PIPERIDINE DERIVATES

Author(s)
S. Intasar Hussain Taqvi
Institute/University/Department Details
Department of Pharmacology/ University of Karachi
Session
2003
Subject
Number of Pages
418
Keywords (Extracted from title, table of contents and abstract of thesis)
piperidine, peptide opioids, analgesics, arrhythmogenesis, cardioactive drugs, opioid receptors

Abstract
Synthetic, semi-synthetic and peptide opioids are well known as analgesics. To date the majority of the reported studies have been in neuronal tissues, to understand mechanism of action of analgesia and to produce better, safer and more potent analgesic. The pharmacological profile of most opioid agents on the heart and cardiovascular system remains uncharacterized to a large degree as yet. Most of the studies reporting the effects on cardiovascular system reveal the involvement of central or peripheral nervous system. Very few studies are reported in the literature which illustrate the ro1e of opioid receptor-dependent or independent in several cardiovascular pathophysiological states including hypertension, heart failure and ischemic arrhythmogenesis. In many instances it appears that the effects of opioid agonist and antagonist in different cardiovascular disease model may be mediated by opioid receptor-independent acuons of the drugs. Very often, the modulation of Ca++ through calcium channel or release of cellular bond clacium have been ignored, so the present studies are also unique in this regard.

The cardiovascular profile of phenacyl derivatives of piperidine ring having hydroxyl or acetyl group are not found in the surveyed literature which reports reporting the cardiovascular activity of these compounds. The limitations of the existing cardiovascular drugs and widespread prevalence of cardiovascular diseases led to design the present studies. The new derivatives are studied in Langendorf’s heart. This technique has been enjoying the place of validity to test new analogs for cardioactivity. Similarly, intestinal and vascular smooth muscle preparations are used to delineate the mode of action which are well established methods for this purpose, and have received considerable attentions and favour by the research workers involved in cardiovascular research.

The results of the present studies reveal that these compounds are found to be cardioactive. Specific opioid receptor-independent effects have been observed. Dose-dependent negative chronotropic activity, positive inotropic effect at certain doses and the disappearance of arrhythmic changes at higher doses are not only the distinguishing feature of test compounds but may have certain clinical significance In cardiovascular disorders when positive inotropic effects and negative chronotropic activity along with anti-arrhythmic actions are desirable.

Voltage-operated and receptor-operated clacium channels are blocked by these compounds. This offers another benefit over existing β-and α-blockers and vasodilators.

However, further study of established the clinical significance of these compounds are highly favored which may open a new era in the management of cardiovascular pathologies, which requires the drugs with unique actions.

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4083.44 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
245.12 KB
2 1 Introduction 1
424.01 KB
  1.1 Growing Need Of Cardiovascular Drugs 1
  1.2 Methods Of Pre-Clinical Studies Of Cardioactive Drugs 29
  1.3 Significance Of Piperidine Compounds In Cardiovascular Therapy 45
3 2 An Insight In The Cardiovascular Pharmacology Of Opioids 50
301.52 KB
  2.1 Types Of Opioid Receptors 51
  2.2 Binding Of Opioids To Receptors 52
  2.3 Tissue Distribution Of Receptors 54
  2.4 Role Of Endogenous Peptides 57
  2.5 Role Of Synthetic Opioids 58
  2.6 Role In The Coronary Vessels 65
  2.7 Role In Hypertension 66
  2.8 Diuretic Effect Of Opioids In Hypertension 67
  2.9 Role In Heart Failure 68
  2.10 Role In Ischaemic Pre-Conditioning 70
  2.11 Role In Ischaemic Arrhythmogenesis 74
  2.12 Effect On Endocrine System 78
  2.13 Structure Activity Relationship 79
4 3 Literature Review 81
171.54 KB
5 4 Materials And Methods 99
105.33 KB
  4.1 Langendorff’s Heart 99
  4.2 Experiments On Smooth Muscles 105
6 5 Results And Discussions 111
2368.75 KB
  5.1 Pharmacological Evaluation Of Compound A 111
  5.2 Pharmacological Evaluation Of Compound B 144
  5.3 Pharmacological Evaluation Of Compound C 182
  5.4 Pharmacological Evaluation Of Compound D 219
  5.5 Pharmacological Evaluation Of Compound E 255
  5.6 Pharmacological Evaluation Of Compound G 291
7 6 Conclusion 315
37.92 KB
8 7 References 319
591.71 KB
9 8 Appendices 387
360.16 KB