see also:

• pharmacology main index
• parasympathetics
• inotropes
• sympNS
• parasympNS

• Sympathomimetics are drugs that mimic the actions of the naturally occurring catecholamines with beta-phenylethylamine being the parent compound:

(benzene ring-CH2-CH2-NH2).

• The greatest sympathomimetic activity is when 2 C atoms separate the ring from the amino group & OH groups are on the 3,4 positions of the benzene ring making it a catecholamine.
• When the benzene is replaced by a catechol ring (3,4-diOHbenzene), then the drug is called a catecholamine:
  • adrenaline / epinephrine, noradrenaline / norepinephrine, dopamine, dobutamine, isoprenaline;
• Increasing the alkyl substituent on the amino group increases beta activity (eg. isoprenaline) and if 3,5-diOH benzene as well then beta2 selectivity (eg. terbutaline, salbutamol);
• Unsubstituted or alkyl substituted compounds are more lipid soluble as less polar & thus cross blood-brain barrier more readily (eg. ephedrine, amphetamine) but causes loss of direct peripheral sympathomimetic activity.
• Catechol-O-methyltransferase (COMT) in GIT & liver metabolise catechol groups & thus drugs with these are not orally active.
• Non-catecholamines are degraded by MAO, but this is inhibited if there is substitution on the alpha C atom (eg. ephedrine, amphetamine) ⇒ their half-life hours instead of minutes;
• L-rotatory on the beta-C atom increases peripheral activity about 10 ;
• D-rotatory on the alpha-C atom increases CNS activity (eg. d-amphetamine)

• smooth muscle blood vessels to skin, mucosa;
• gland cells (eg. salivary, sweat) (alpha);

• smooth muscle GIT, bronchi, blood vessels to skeletal muscle (beta2);

• inotropic + chronotropic (beta1);

• increased glycogenolysis in liver & skel. muscle;
• liberation of FFA's from adipose tissue;

• respiratory stimulation; increased wakefulness;
• increased psychomotor activity; decreased appetite;

• either inhibitory or facilitatory effect on release of neurotransmitters - physiologically inhibitory > facilitatory

• agonist: phenylephrine, metaraminol (Aramine), noradrenaline / norepinephrine see alpha adrenergic agonists;
• antagonist: prazosin see alpha adrenergic blockers
• Gq ⇒ inc. phospholipase C ⇒ inc. DAG + inc. IP3 ⇒ inc. [Ca]i ⇒ inc. protein kinase C ⇒ other Ca/calmod.inc.
  • ⇒ post-junctional vasc. smooth muscle ⇒ vasoconstriction;
  • ⇒ decreased arterial capacitance; increased diastolic BP; shunt blood
  • ⇒ post-jn. vascular adventitia
  • ⇒ extra-jn. vascaular intima (mainly alpha2 though)
  • ⇒ post-jn. myocardium ⇒ increased inotropy; increased arrythmias
  • ⇒ liver ⇒ glycogenolysis & gluconeogenesis ⇒ hyperglycaemia
  • ⇒ renal Na reabsorption increased via stimulating proximal tubule NHE3 and basolateral NaKATPase
  • ⇒ increased salivary secretion and salivary K+ levels
  • ⇒ genitourinary smooth muscle contraction
  • ⇒ prostate ⇒ alpha 1a contracts smooth muscle and can worsen benign prostatic hyperplasia (BPH) symptoms
  • ⇒ bladder ⇒ alpha 1a bladder neck constriction preventing retrograde ejaculation but also worsens benign prostatic hyperplasia (BPH) symptoms
  • ⇒ mitogenic response in many cells
  • CNS effects: anorexia, etc
• NB. ischemia ⇒ decreased number of alpha1 binding sites ⇒ tolerance

• agonist: clonidine;
• antagonist: Yohimbine;
• ⇒ Gi ⇒ decreased adenylyl cyclase ⇒ decreased [cAMP]i ⇒ decreased cAMP-dep.prot.kinases;
• ⇒ increased inward K decreased voltage-dependent calcium flow
  • ⇒ hyperpolarises cholinergic myenteric neurons ⇒ decreases GIT motility;
• ⇒ post-jn. vasc. sm.muscle ⇒ vasoconstriction;
• ⇒ extra-jn. vasc. intima
• ⇒ pancreatic islets (beta cells) ⇒ decreased insulin secretion;
• ⇒ platelet aggregation;
• ⇒ nerve terminals ⇒ decreased release NA;

• agonist: dobutamine;
• antagonist: metoprolol - see beta adrenergic blockers
• ⇒ Gs ⇒ increased [cAMP] ⇒ increased cAMP-dependent protein kinase
• ⇒ increased voltage-dependent calcium in skeletal & cardiac muscle;
• ⇒ myocardial ⇒ increased inotropy + increased chronotropy ⇒ increased myocardial O2 demand;
• ⇒ Purkinje fibres ⇒ increased AV nodal cond. velocity;
• ⇒ JGM cells ⇒ increased renin secretion;

• see also beta 2 adrenergic agonists
• agonist: terbutaline; salbutamol;
• antagonist: ICI 118551;
• ⇒ Gs as for beta1 but ? not the Ca channel effect;
• ⇒ bronchodilatation;
• ⇒ peripheral vasodilatation;
• ⇒ relaxation of genitourinary & GIT smooth muscle
• ⇒ liver ⇒ glycogenolysis & gluconeogenesis;
• ⇒ skeletal muscle ⇒ glycogenolysis & increased uptake K;
• ⇒ K into cells ⇒ hypokalaemia;

• agonist:
  • mirabegron - used to Rx overactive bladders
• antagonist: CGP 20712A
• ⇒ increased adenylate cyclase
• ⇒ lipolysis in adipose tissue;
• ⇒ relaxes detrusor muscle ⇒ increases urinary bladder capacity

• see dopamine receptors
• agonist: dopamine; 
• antagonist: phenothiazines, haloperidol;
• post-synaptic ⇒ increased adenylyl cyclase ⇒ increased [cAMP]:
  • ⇒ vasodilatation (esp. renal & mesenteric)-⇒ increased GFR; increased RBF; increased Na excretion

• see dopamine receptors
• agonist: dopamine; 
• antagonist: phenothiazines, haloperidol;dopamine receptor blockers
• presynaptic:
  • ⇒ symp.N ⇒ decreased NA release
  • ⇒ autonomic ganglia ⇒ modulate transmission;
  • ⇒ CNS effect on sympathetics ⇒ decreased CNS effect;
  • ⇒ pituitary ⇒ decreased adenylate cyclase
  • ⇒ ? decreased prolactin