Drug Receptors N. S.

Drug Action

Drugs of C.N.S
 Elmhurst College
Nervous System Cholinergic Drugs II Adrenergic Drugs II  Chemistry Department
Cholinergic Drugs I Adrenergic Drugs I Adrenergic Drugs III  Virtual ChemBook

Adrenergic Drugs I

Introduction:

Adrenergic nerves release norepinephrine as the neurotransmitter for the sympathetic nervous system. The sympathetic system activates and prepares the body for vigorous muscular activity, stress, and emergencies. Adrenergic drugs stimulate the adrenergic nerves directly by mimicking the action of norepinephrine or indirectly by stimulating the release of norepinephrine.

Therapeutically, these drugs are used to combat life-threatening disorders, which include acute attacks of bronchial asthma, shock, cardiac arrest, and allergic reactions. In addition these drugs are used in nasal decongestants and appetite suppressants.

Adrenergic Nerve Transmissions:

Adrenergic nerves release the neurotransmitters: Norepinephrine (noradrenaline, NE), epinephrine, EP, and dopamine DA. The synthesis of the neurotransmitters DA and NE and EP and the hormones NE and EP takes place by a pathway that involves 5 enzymes. Tyrosine is generally considered the starting point to synthesize DOPA (1a), DA (1b), and NE (1c). Norepinephrine is stored at (2).

Norepinephrine is released from the nerve ending in response to a nerve impulse or drug (3). NE interacts with alpha and beta receptor sites at (4). Its receptor action is terminated by recapture and storage in the original nerve ending or inactivated by an enzyme. For example chloropheniramine, an antihistamine, can inhibit the mechanism for uptake and recapture of norepinephrine.

There are at least two adrenergic receptor sites (alpha or beta). Norepinephrine activates primarily alpha receptors and epinephrine activates primarily beta receptors, although it may also activate alpha receptors. Stimulation of alpha receptors is associated with constriction of small blood vessels in the bronchial mucosa and relaxation of smooth muscles of the intestinal tract. Beta receptor activation relaxes bronchial smooth muscles which cause the bronchi of the lungs to dilate.

In addition beta receptor stimulatory effects cause an increase in the rate and force of heart contractions. As a result increased amounts of blood leave the heart and is diverted from nonactive organs to areas that actively participate in the body's reaction to stress such as skeletal muscles, brain, and liver.

Adrenergic Receptor Sites:

Alpha Receptor Site: Important features of the site include in order of importance:

1) An anionic site - which binds the positive ammonium group.

2) One hydrogen bonding area

3) A flat area non-polar area for the aromatic ring.

Beta Receptor Site: Important features of the site include in order of importance - also see the graphic on the left:

1) An anionic site - shown as Asp anionic negative acid group which binds the positive ammonium group.

2) Two hydrogen bonding areas - shown as two Serine with alcohol (OH) groups hydrogen bonding to the phenol OH groups of the NE.

3) A flat area non-polar area for the aromatic ring.

 Tissue   Receptor Subtype  Agonists  Antagonists
 Heart   beta1   NE, EP, dobutamine, xamoterol atenolol, metoprolol.
 Adipose tissue   beta1, beta 3?    
Vascular Smooth Muscle  beta 2  EP, salbutamol, terbutaline, salmeterol butoxamine
Airway Smooth Muscle   beta 2  terbutaline, salbutamol, salmeterol and zinterol, butoxamine
 Smooth muscle contraction  alpha 1  NE, EP, phenylephrine, oxymetazoline) prazosin, doxazocin
 Inhibition of
transmitter release Hypotension, anaesthesia, Vasoconstriction
 alpha 2 clenbuterol, alpha-methylnoradrenaline, dexmedetomidine, and mivazerol, clonidine, clenbuterol yohimbine, idazoxan, atipamezole, efaroxan, and rauwolscine

Receptor Sites
 alpha-receptor  beta-receptor
 Vasoconstriction  vasodilation (b2)
 iris dilation  cardioacceleration (b1)
 intestinal relaxation  intestinal relaxation (b2)
 intestinal sphincter
contraction
 uterus relaxation(b2)
 bladder sphincter contraction  bronchodilation (b2)