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AN EVALUATION OF THE PROBABLE CHOLINERGIC EFFECTS OF BDF 8503.

10,000

ATTENTION:

BEFORE YOU READ THE CHAPTER ONE/ABSTRACT OF THE PROJECT TOPIC BELOW, PLEASE READ THE INFORMATION BELOW.THANK YOU!

 

INFORMATION:

YOU CAN GET THE COMPLETE PROJECT OF THE TOPIC BELOW. THE FULL PROJECT COSTS N10,000 ONLY.

THE FULL INFORMATION ON HOW TO PAY AND GET THE COMPLETE PROJECT IS AT THE BOTTOM OF THIS PAGE. OR YOU CAN CALL: 08137701720

 

 

AN EVALUATION OF THE PROBABLE CHOLINERGIC EFFECTS OF BDF 8503.

 

 

TABLE OF CONTENT

DECLARATION

DEDICATION

ACKNOWLEDGEMENT

TABLE OF CONTENTS

ABSTRACTS

CHAPTER ONE

LITERATURE REVIEW

  • GENERAL INTRODUCTION
  • ACETYLCHOLINE
  • PRAZOBIN
  • PIRENZEPINE
  • BDF 8503
  • AIMS OF PROJECT

CHAPTER TWO

2.1      MATERIALS

2.2      METHOD

2.3      THE GUINEA – PIG ILEUM

2.4      PRECAUTIONS TAKEN

2.5      STATISTICS

            CHAPTER THREE

3.1      RESULTS

            CHAPTER FOUR

4.1      DISCUSSION

4.2      MODEL

4.3      SUMMARY AND CONCLUSION

REFERENCES

 

 

ABSTRACTS

  • The effects of BDF 8503 (10-6m) on the response of the guinea – pig ileum to Ach. Were investigated.
  • The effects of 10-8m – 10-7m of prezosin on the Ach contractile response on the guinea –pig ileum were also investigated.
  • BDF 8503 potentiated the contractile response to Ach. This was evidenced by the shift of the dose-response curve to the left, the increase in Emax and the fall in Ec50. An inverse relationship between the doses of BDF 8503 used and the degree of potentiation was observed. No change in baseline was observed.
  • Prazosin (10-8-10-7m) produced similar results as was obtained with BDF 8503, in addition to an increase in baseline.
  • BDF 8503 still potentiated responses to Ach when coadministered with prazosin. Prazosin was allowed a contact time of 15 minutes before BDF 8503 was added.
  • BDF 8503 potential responses to Ach when coadministered with prazosin and pirenzepine.
  • These results suggest that: (a) the potentiating effects of BDF 8503 may be mediated via a selective 1 – adrendceptor blockade. (b) a non 1 – adrenoceptor mechanism, such as the sensitization of muscarinic receptors or activation of other unknown receptors, may be involved.

Further investigations, using an        1 agonist such as phenylephrine, M1– cholinoceptor agonist such as MCN – A – 343 and an M2 – cholinoceptor antagonist such as atropine,. Have been suggested.

 

 

 

 

 

 

 

 

 

 

 

CHAPTER ONE

LITERATURE REVIEW

  • GENERAL INTRODUCTION

The introduction of a new drug candidate is usually followed by a period of screening for characterization of its pharmacologival profile. The screening for characterization of its pharmacological profile. The screening is done first in animals, and then in man.

The choice of a screening procedure is more often influenced by: the reliability and sensitivity of the test; the simplicity of the test; and the type of drug being studied. Indeed, no screening procedure can be perfect. Hence, it is imperative that anyone performing a screening test should be vigilant for borderline results and for results indicating and borderline results for results indicating an inactive substance even when one strongly suspects that activity may be present.

Generally, it is better to use a screening test which gives a few type II errors (accepting and inactive substance as being active), this is because, if a substance has no true activity but is shown by a test to be active (type II error), sooner or later as testing with the substance is continued, its inactivity will be revealed. Although some time may be wasted in studying the compound, in the end the investigator is not misled. Conversely, when an active substance is rejected being inactive (type I error), it may result in its removal from further study, so that its activity will remain forever undetected. One important approach in reducing both types of error is to increase the sample size, which may or may not be possible.

An important factor common to all screening methods is that they require the exercise of judgement and discretion on the part of the investigator. The quality of such a judgement would invariably depend on the investigators knowledge of the tools used in his investigation. Hence, a brief summary of the pharmacology of acetylcholine (Ach), prazosin and pirezepine – which are the tools used in this study on BDF 8503 – is imperative.

  • acetylcholine (Ach)

Ach, which was first synthesized by Baeyer in 1867, is an endogenous neutransmitter found in many parts of the body such as:

  • autonomic effector sites innervated by post-ganglionic parasympathetic fibres;
  • sympathetic and parasympathetic ganglion cells and the adrenal medullar, innervated by pre-ganglionic autonomic fibres;
  • moto end-plates on skeletal muscles, innervated by somatic motor nerves; and
  • certain synapses within the central nervous system (CNS). The amount of Ach in the body has not been assayed. However, it has been estimated that the guinea=pig intestine, when assayed for Ach on frog rectus muscle, contains 54.8n mole/g of ach (Feldberg and Lin, 1950).

STRUCTURE/STRUCTURE – ACTIVITY RELATIONSHIPS:

1            2      3     4          5      6

(CH3)3             N+– CH2– CH2-o – C – CH3

 

The structure of Ach is shown above. Substitution of the (CH3) moiety at position 1 with (NH2) group, as exemplified by carbachol, leads to a loss in susceptibility to cholinesterase reduction. Addition of a methyl group at position 4 results in a reduction in both nicotinic activity and susceptibility to cholinesterase reduction. This is also exemplified by methacholine – a derivative of acetylcholine (Watanabe, 1984).

Mechanisms of action:

The pharmacological effects of Ach are mediated via its binding to muscarinic and nicotinic receptors. There are at least 3 subtypes of muscarinic receptors termed M1 M2, and M3 (De Jorge et al; 1986).

M1 receptors are found in the cerebral cortex and to a lesser extent in autonomic ganglionic cells. This receptor has a high affinity for pirenzepine. Conversely, N2 receptors have a low pirenzepine affinity but high methoctramine and AF- Dx116 affinity. M2 receptors are found in the heart, central neutral neurones, as well as in the guinea-pig ileum (De Jorge et al., 1986). M3 receptors abound in gland tissues, and have low affinity for AF-Dx 116 and methctramine. An atypical muscarinic receptor has recently been described by Michel et al. (1988).

The cellular events following the interaction of Ach with its muscarine receptors are not well understood. Available evidence however, suggest that it might involve one or more of the following primary events:

  • an increase in concentration of cyclic guanosine mono-phosphate (CGMP), presumably by activating guanylate cyclase which catalyses the conversion of guanasine triphosphate (GTP) to CGMP;
  • an increase in inositol phospholipid turnover in cellular membranes;
  • inhibition of adenyl cyclase activity in specific organs, that is the heart.

The interaction of Ach with nicotinic receptors (found in the autonomic ganglia, striated muscles and central neurones), results in a conformational change in the receptors protein that allows Na+ and k+ to diffuse

Ach has a broad pharmacological action in the organs and systems of the body. These actions shall be considered systemically.

CARDIOVASCULAR SYSTEM (CVS):

The main effects of Ach on the cvs are the reduction in peripheral vascular resistance and changes in heart rate. Intravenous infusions of minimal effective doses of Ach in man (20-50ng/min) causes vasodilatation which results in a reduction in blood pressure, and if often accompanied by a reflex increase in heart rate. Larger doses produce bradycardia and decreased conduction velocity through the atrioventricular node, in addition to the hypotensive effect.

GASTRO INTESTINAL TRACK:

Ach stimulates the parasympathetic system to the gut and causes an increase in secretory as well as motor activity. The salivary and gastric glands are strongly stimulated – the intestinal glands are strongly stimulated – the intestinal glands less so. Peristaltic activity is increased throughout the gut and most sphincters are relaxed. Similar effects may occur in the guinea pig intestine.

The instillation of Ach into the conjunctiva sac causes contraction of the smooth muscles of the iris Intra-ocular pressure is also decreased by facilitating the out flow of aqueous homor into the canal of Schlem which drains the anterior chamber of the age.

RESPIRATORY SYSTEM:

Ach stimulates the glandular secretions of the tracheobronchial glands. It also stimulates the contraction of the smooth muscles of the brochial tree.

GENITOURINARY TRACT :

The detrusor muscle is stimulated to contract while the trigone and sphincter muscle of the bladder are relaxed – this promoting voiding of urine.

Neuromuscular junction:

When Ach is applied directly (by iontophoresis or by intra-arterial injection), an immediate depolarization of the end-plate results. This causes an increase in permeability to Na+ and results in a contractile response.

Central nervous system (CVS)

The brain has a preponderance of muscarinic to nicotinic receptors, while the converse is the case in the spinal cord. Despite this, however, nicotine has very important effects on the brain stem and cortex. In moderate doses, Ach acts on nicotinic receptors and causes a mild alerting effect on the CNS. Higher doses cause tremor, emesis and stimulation of the respiratory centre, while still higher doses cause convulsion which might terminate in fatal coma.

Pharmacokinetics:

Ach is rarely used therapeutically. However, a 1% solution of Ach is available for sue in cataract extractions and certain other surgical procedures on the anterio segment of the eye when it isa desired to produce miosis rapidly.

  • PRAZOSIN

Prazosin is a selective d1 – adrenoceptor anatagonost effective in hypertension. It has the chemical structure shown below.

Mode of action:

Prazosin selectively antagonise d1 – (post-synaptic) adrenoceptors and causes peripheral arteriolar vasodilation which leads to a fall in blood pressure in hypertension, and a decrease in after-load in cardiac failure.

The hypotension produced by tarchycardia because d2 (presynaptic) adrenoceptors are not affected by prazosin, which, when otherwise blocked, would cause further release of noradrenamone and subsequent tarchycardia. This is observed with the non-selective d (- adrenoceptor antagonosts such as phetolamone and phenoxybenzamine.

Phosphodiesterae and dopamine – B – dydroxylase inhibition occurs with prazosin, but only at concentrations much higher than are found during therapy, and hence might not contribute to its clinical effects (Grahame-smith and Aronson, 1985).

ADVERSE EFFECTS:

Dizziness and less of consciousness may occur following the first dose of prazosin, due to profound hypotension (Grahame-smith and aronson, 1985). This effect is especially marked in patients taking diuretics or  B-adrenoceptor antagonists. Other common adverse effects are: other common adverse effects are: dry mouth; headache; postural dizziness; and tarchycardia.

USES

Prazosin is used in chronic heart failure and hypertension.

  • PIRENZEPINE

This drug is a tricyclic benzodiazepine derivative having a molecular weight of 424.3 and the chemical formula shown below:

C19H212N5O21 2 HCL.

It was Goyal and Raltan (1978), on the basis of a study with the selective muscarinic agonist _ MCN-A-343, who first proposed the existence of M1-receptors on inhibitory neurones in the oesophagus of the opossum. This, they subsequently confirmed in 1984, using pirenzepine. Other workers have also shown that pirezenpine hs a low affinity for human gut-smooth muscle M1 receptors, and inhibits colonic contractile pressure in man only at high plasma levels. Intravenous doses of atropine and pirenzepine are equipotent with respect t oinhibition of gastric secretion (Abrahamson, et al;. 1985).

Low doses of pirenzepine (0.1-1.0 nM) significantly enhances peristalsis in the guinea-pig ileum, whereas larger concentrations causes inhibition (Schworrer and killbinger, 1988). Since stimulation of ileal M1 receptors have been demonstrated to be inhibitory (Schuurkes el al 1988). Since stimulation of ileum M1 receptors have been demonstrated to be inhibitory (Schuurkes at. Al 1988), and blocker of M2 receptors t obe inhibitory on persistatic activity (Schworer and Kilbinger, 1988), it has been suggested that low doses of pirenzepine selectively blocks M1 receptors while higher doses block M2 receptors as well (Schworer and Kilbinger, 1988).

Evidence for ZM1-receptors on enteric nerve cells have been provided by in situmotility studies; binding studies; autoradiography; in vitro Ach release; and in vivo motility studies (Bettrarello, 1985). Pirenzepine is used therapeutically in peptic ulcers and non-ulcer dyspepsia.

  • BDF 8503

This is pale yellow powder of molecular weight 411.51 and the chemical formula:

C22H29 N5o3

It is thought to be a selective di adrenoceptor antagonist, more potent and having a longer duration of action than prazosin. It has a PA2 of 9.2. is still undergoing trial-0hence it s literature is scanty.

1.6 AIMS OF PROJECT

BDF 8503 had been shown in a previous study to potentiate the contractile response of the guinea – pig ileum to Ach (Amarachukwu, personal communication, (1988). The aims of this study therefore, were:

  • To confirm previous observations of the effects of BDF 8503 on Ach contractile response;
  • To elucidate the mechanism for the above potentiation of Ach – induced contratile responses;
  • To compare these effects with those prazosin, a known 1 – adrenoceptors antagonist in order to determine whether this properties is common to  1 blockers or an additional properties of BDF 8503.

 

 

HOW TO GET THE FULL PROJECT WORK

 

PLEASE, print the following instructions and information if you will like to order/buy our complete written material(s).

 

HOW TO RECEIVE PROJECT MATERIAL(S)

After paying the appropriate amount (#10,000) into our bank Account below, send the following information to 08137701720

(1)    Your project topics

(2)     Email Address

(3)     Payment Name

(4)    Teller Number

We will send your material(s) after we receive bank alert

 

BANK ACCOUNTS

Account Name: AMUTAH DANIEL CHUKWUDI

Account Number: 0046579864

Bank: GTBank.

 

OR

Account Name: AMUTAH DANIEL CHUKWUDI

Account Number: 2023350498

Bank: UBA.

 

 

NOTE:

YOU CAN ALSO MAKE A TRANSFER PAYMENT

 

FOR MORE INFORMATION, CALL:

08137701720

 

AFFILIATE LINKS:

www.easyprojectmaterials.com

www.easyprojectmaterials.net.ng

www.easyprojectsmaterials.net.ng

www.easyprojectsmaterial.net.ng

www.easyprojectmaterial.net.ng

 

 

 

 

 

 

 

ATTENTION:

BEFORE YOU READ THE CHAPTER ONE/ABSTRACT OF THE PROJECT TOPIC BELOW, PLEASE READ THE INFORMATION BELOW.THANK YOU!

 

INFORMATION:

YOU CAN GET THE COMPLETE PROJECT OF THE TOPIC BELOW. THE FULL PROJECT COSTS N10,000 ONLY.

THE FULL INFORMATION ON HOW TO PAY AND GET THE COMPLETE PROJECT IS AT THE BOTTOM OF THIS PAGE. OR YOU CAN CALL: 08137701720

 

 

 

 

AN EVALUATION OF THE PROBABLE CHOLINERGIC EFFECTS OF BDF 8503.

TABLE OF CONTENT

DECLARATION

DEDICATION

ACKNOWLEDGEMENT

TABLE OF CONTENTS

ABSTRACTS

CHAPTER ONE

LITERATURE REVIEW

  • GENERAL INTRODUCTION
  • ACETYLCHOLINE
  • PRAZOBIN
  • PIRENZEPINE
  • BDF 8503
  • AIMS OF PROJECT

CHAPTER TWO

2.1      MATERIALS

2.2      METHOD

2.3      THE GUINEA – PIG ILEUM

2.4      PRECAUTIONS TAKEN

2.5      STATISTICS

            CHAPTER THREE

3.1      RESULTS

            CHAPTER FOUR

4.1      DISCUSSION

4.2      MODEL

4.3      SUMMARY AND CONCLUSION

REFERENCES

 

 

ABSTRACTS

  • The effects of BDF 8503 (10-6m) on the response of the guinea – pig ileum to Ach. Were investigated.
  • The effects of 10-8m – 10-7m of prezosin on the Ach contractile response on the guinea –pig ileum were also investigated.
  • BDF 8503 potentiated the contractile response to Ach. This was evidenced by the shift of the dose-response curve to the left, the increase in Emax and the fall in Ec50. An inverse relationship between the doses of BDF 8503 used and the degree of potentiation was observed. No change in baseline was observed.
  • Prazosin (10-8-10-7m) produced similar results as was obtained with BDF 8503, in addition to an increase in baseline.
  • BDF 8503 still potentiated responses to Ach when coadministered with prazosin. Prazosin was allowed a contact time of 15 minutes before BDF 8503 was added.
  • BDF 8503 potential responses to Ach when coadministered with prazosin and pirenzepine.
  • These results suggest that: (a) the potentiating effects of BDF 8503 may be mediated via a selective 1 – adrendceptor blockade. (b) a non 1 – adrenoceptor mechanism, such as the sensitization of muscarinic receptors or activation of other unknown receptors, may be involved.

Further investigations, using an        1 agonist such as phenylephrine, M1– cholinoceptor agonist such as MCN – A – 343 and an M2 – cholinoceptor antagonist such as atropine,. Have been suggested.

 

 

 

 

 

 

 

 

 

 

 

CHAPTER ONE

LITERATURE REVIEW

  • GENERAL INTRODUCTION

The introduction of a new drug candidate is usually followed by a period of screening for characterization of its pharmacologival profile. The screening for characterization of its pharmacological profile. The screening is done first in animals, and then in man.

The choice of a screening procedure is more often influenced by: the reliability and sensitivity of the test; the simplicity of the test; and the type of drug being studied. Indeed, no screening procedure can be perfect. Hence, it is imperative that anyone performing a screening test should be vigilant for borderline results and for results indicating and borderline results for results indicating an inactive substance even when one strongly suspects that activity may be present.

Generally, it is better to use a screening test which gives a few type II errors (accepting and inactive substance as being active), this is because, if a substance has no true activity but is shown by a test to be active (type II error), sooner or later as testing with the substance is continued, its inactivity will be revealed. Although some time may be wasted in studying the compound, in the end the investigator is not misled. Conversely, when an active substance is rejected being inactive (type I error), it may result in its removal from further study, so that its activity will remain forever undetected. One important approach in reducing both types of error is to increase the sample size, which may or may not be possible.

An important factor common to all screening methods is that they require the exercise of judgement and discretion on the part of the investigator. The quality of such a judgement would invariably depend on the investigators knowledge of the tools used in his investigation. Hence, a brief summary of the pharmacology of acetylcholine (Ach), prazosin and pirezepine – which are the tools used in this study on BDF 8503 – is imperative.

  • acetylcholine (Ach)

Ach, which was first synthesized by Baeyer in 1867, is an endogenous neutransmitter found in many parts of the body such as:

  • autonomic effector sites innervated by post-ganglionic parasympathetic fibres;
  • sympathetic and parasympathetic ganglion cells and the adrenal medullar, innervated by pre-ganglionic autonomic fibres;
  • moto end-plates on skeletal muscles, innervated by somatic motor nerves; and
  • certain synapses within the central nervous system (CNS). The amount of Ach in the body has not been assayed. However, it has been estimated that the guinea=pig intestine, when assayed for Ach on frog rectus muscle, contains 54.8n mole/g of ach (Feldberg and Lin, 1950).

STRUCTURE/STRUCTURE – ACTIVITY RELATIONSHIPS:

1            2      3     4          5      6

(CH3)3             N+– CH2– CH2-o – C – CH3

 

The structure of Ach is shown above. Substitution of the (CH3) moiety at position 1 with (NH2) group, as exemplified by carbachol, leads to a loss in susceptibility to cholinesterase reduction. Addition of a methyl group at position 4 results in a reduction in both nicotinic activity and susceptibility to cholinesterase reduction. This is also exemplified by methacholine – a derivative of acetylcholine (Watanabe, 1984).

Mechanisms of action:

The pharmacological effects of Ach are mediated via its binding to muscarinic and nicotinic receptors. There are at least 3 subtypes of muscarinic receptors termed M1 M2, and M3 (De Jorge et al; 1986).

M1 receptors are found in the cerebral cortex and to a lesser extent in autonomic ganglionic cells. This receptor has a high affinity for pirenzepine. Conversely, N2 receptors have a low pirenzepine affinity but high methoctramine and AF- Dx116 affinity. M2 receptors are found in the heart, central neutral neurones, as well as in the guinea-pig ileum (De Jorge et al., 1986). M3 receptors abound in gland tissues, and have low affinity for AF-Dx 116 and methctramine. An atypical muscarinic receptor has recently been described by Michel et al. (1988).

The cellular events following the interaction of Ach with its muscarine receptors are not well understood. Available evidence however, suggest that it might involve one or more of the following primary events:

  • an increase in concentration of cyclic guanosine mono-phosphate (CGMP), presumably by activating guanylate cyclase which catalyses the conversion of guanasine triphosphate (GTP) to CGMP;
  • an increase in inositol phospholipid turnover in cellular membranes;
  • inhibition of adenyl cyclase activity in specific organs, that is the heart.

The interaction of Ach with nicotinic receptors (found in the autonomic ganglia, striated muscles and central neurones), results in a conformational change in the receptors protein that allows Na+ and k+ to diffuse

Ach has a broad pharmacological action in the organs and systems of the body. These actions shall be considered systemically.

CARDIOVASCULAR SYSTEM (CVS):

The main effects of Ach on the cvs are the reduction in peripheral vascular resistance and changes in heart rate. Intravenous infusions of minimal effective doses of Ach in man (20-50ng/min) causes vasodilatation which results in a reduction in blood pressure, and if often accompanied by a reflex increase in heart rate. Larger doses produce bradycardia and decreased conduction velocity through the atrioventricular node, in addition to the hypotensive effect.

GASTRO INTESTINAL TRACK:

Ach stimulates the parasympathetic system to the gut and causes an increase in secretory as well as motor activity. The salivary and gastric glands are strongly stimulated – the intestinal glands are strongly stimulated – the intestinal glands less so. Peristaltic activity is increased throughout the gut and most sphincters are relaxed. Similar effects may occur in the guinea pig intestine.

The instillation of Ach into the conjunctiva sac causes contraction of the smooth muscles of the iris Intra-ocular pressure is also decreased by facilitating the out flow of aqueous homor into the canal of Schlem which drains the anterior chamber of the age.

RESPIRATORY SYSTEM:

Ach stimulates the glandular secretions of the tracheobronchial glands. It also stimulates the contraction of the smooth muscles of the brochial tree.

GENITOURINARY TRACT :

The detrusor muscle is stimulated to contract while the trigone and sphincter muscle of the bladder are relaxed – this promoting voiding of urine.

Neuromuscular junction:

When Ach is applied directly (by iontophoresis or by intra-arterial injection), an immediate depolarization of the end-plate results. This causes an increase in permeability to Na+ and results in a contractile response.

Central nervous system (CVS)

The brain has a preponderance of muscarinic to nicotinic receptors, while the converse is the case in the spinal cord. Despite this, however, nicotine has very important effects on the brain stem and cortex. In moderate doses, Ach acts on nicotinic receptors and causes a mild alerting effect on the CNS. Higher doses cause tremor, emesis and stimulation of the respiratory centre, while still higher doses cause convulsion which might terminate in fatal coma.

Pharmacokinetics:

Ach is rarely used therapeutically. However, a 1% solution of Ach is available for sue in cataract extractions and certain other surgical procedures on the anterio segment of the eye when it isa desired to produce miosis rapidly.

  • PRAZOSIN

Prazosin is a selective d1 – adrenoceptor anatagonost effective in hypertension. It has the chemical structure shown below.

Mode of action:

Prazosin selectively antagonise d1 – (post-synaptic) adrenoceptors and causes peripheral arteriolar vasodilation which leads to a fall in blood pressure in hypertension, and a decrease in after-load in cardiac failure.

The hypotension produced by tarchycardia because d2 (presynaptic) adrenoceptors are not affected by prazosin, which, when otherwise blocked, would cause further release of noradrenamone and subsequent tarchycardia. This is observed with the non-selective d (- adrenoceptor antagonosts such as phetolamone and phenoxybenzamine.

Phosphodiesterae and dopamine – B – dydroxylase inhibition occurs with prazosin, but only at concentrations much higher than are found during therapy, and hence might not contribute to its clinical effects (Grahame-smith and Aronson, 1985).

ADVERSE EFFECTS:

Dizziness and less of consciousness may occur following the first dose of prazosin, due to profound hypotension (Grahame-smith and aronson, 1985). This effect is especially marked in patients taking diuretics or  B-adrenoceptor antagonists. Other common adverse effects are: other common adverse effects are: dry mouth; headache; postural dizziness; and tarchycardia.

USES

Prazosin is used in chronic heart failure and hypertension.

  • PIRENZEPINE

This drug is a tricyclic benzodiazepine derivative having a molecular weight of 424.3 and the chemical formula shown below:

C19H212N5O21 2 HCL.

It was Goyal and Raltan (1978), on the basis of a study with the selective muscarinic agonist _ MCN-A-343, who first proposed the existence of M1-receptors on inhibitory neurones in the oesophagus of the opossum. This, they subsequently confirmed in 1984, using pirenzepine. Other workers have also shown that pirezenpine hs a low affinity for human gut-smooth muscle M1 receptors, and inhibits colonic contractile pressure in man only at high plasma levels. Intravenous doses of atropine and pirenzepine are equipotent with respect t oinhibition of gastric secretion (Abrahamson, et al;. 1985).

Low doses of pirenzepine (0.1-1.0 nM) significantly enhances peristalsis in the guinea-pig ileum, whereas larger concentrations causes inhibition (Schworrer and killbinger, 1988). Since stimulation of ileal M1 receptors have been demonstrated to be inhibitory (Schuurkes el al 1988). Since stimulation of ileum M1 receptors have been demonstrated to be inhibitory (Schuurkes at. Al 1988), and blocker of M2 receptors t obe inhibitory on persistatic activity (Schworer and Kilbinger, 1988), it has been suggested that low doses of pirenzepine selectively blocks M1 receptors while higher doses block M2 receptors as well (Schworer and Kilbinger, 1988).

Evidence for ZM1-receptors on enteric nerve cells have been provided by in situmotility studies; binding studies; autoradiography; in vitro Ach release; and in vivo motility studies (Bettrarello, 1985). Pirenzepine is used therapeutically in peptic ulcers and non-ulcer dyspepsia.

  • BDF 8503

This is pale yellow powder of molecular weight 411.51 and the chemical formula:

C22H29 N5o3

It is thought to be a selective di adrenoceptor antagonist, more potent and having a longer duration of action than prazosin. It has a PA2 of 9.2. is still undergoing trial-0hence it s literature is scanty.

1.6 AIMS OF PROJECT

BDF 8503 had been shown in a previous study to potentiate the contractile response of the guinea – pig ileum to Ach (Amarachukwu, personal communication, (1988). The aims of this study therefore, were:

  • To confirm previous observations of the effects of BDF 8503 on Ach contractile response;
  • To elucidate the mechanism for the above potentiation of Ach – induced contratile responses;
  • To compare these effects with those prazosin, a known 1 – adrenoceptors antagonist in order to determine whether this properties is common to  1 blockers or an additional properties of BDF 8503.

 

 

HOW TO GET THE FULL PROJECT WORK

 

PLEASE, print the following instructions and information if you will like to order/buy our complete written material(s).

 

HOW TO RECEIVE PROJECT MATERIAL(S)

After paying the appropriate amount (#10,000) into our bank Account below, send the following information to 08137701720

(1)    Your project topics

(2)     Email Address

(3)     Payment Name

(4)    Teller Number

We will send your material(s) after we receive bank alert

 

BANK ACCOUNTS

Account Name: AMUTAH DANIEL CHUKWUDI

Account Number: 0046579864

Bank: GTBank.

 

OR

Account Name: AMUTAH DANIEL CHUKWUDI

Account Number: 2023350498

Bank: UBA.

 

 

NOTE:

YOU CAN ALSO MAKE A TRANSFER PAYMENT

 

FOR MORE INFORMATION, CALL:

08137701720

 

AFFILIATE LINKS:

www.easyprojectmaterials.com

www.easyprojectmaterials.net.ng

www.easyprojectsmaterials.net.ng

www.easyprojectsmaterial.net.ng

www.easyprojectmaterial.net.ng