Enzymatic destruction properties

Some of the indirectly acting adrenomimetic amines are used primarily for their vasoconstrictive properties. They are applied locally to the nasal mucosa or to the eye. Other amines are used as bronchodilators, while still others are used exclusively for their ability to stimulate the CNS. Many noncatecholamine adrenomimetic amines resist enzymatic destruction, have prolonged actions, and are orally effective. The indirectly acting drugs are effective only when given in large doses, and they often produce tachyphylaxis. 

The actions of acetylcholine released from autonomic and somatic motor nerves are terminated by enzymatic destruction of the molecule. Hydrolysis is accomplished by the action of acetylcholinesterase, which is present in high concentrations in cholinergic synapses. The indirect-acting cholinomimetics have their primary effect at the active site of this enzyme, although some also have direct actions at nicotinic receptors. The chief differences between members of the group are chemical and pharmacokinetic—their pharmacodynamic properties are almost identical. 

In the preparation of semisynthetic cephalosporins, the following improvements are sought (a) increased acid stability, (b) improved pharmacokinetic properties, particularly better oral ab.sorption, ic) broadened antimicrobial spectrum. (d) increased activity agaiast resistant microorganisms (as a result of resistance to enzymatic destruction, improved penetration. increased receptor affinity, etc.), (e) decreased allergenicity, and (f) increased tolerance after parenteral administration. 

The esterification of the free -COOH terminus of pHAs by fatty alcohol enhances their physical properties, namely, the viscosity is lowered and VI increased with low melting temperature characteristics retained (12,24). The formation of an ester bond between a pHA chain and fatty alcohol can occur chemically (12,30) or enzymatically without destruction of the pHA s ester bonds (24). In addition, Hayes and Kleiman successfully esterified di- and poly(hydoxy acid) synthesized chemically to the hydroxyls of 1,10-decanediol via biocatalysis at high yield (24). The resultant materials had melting point temperatures < -17°C and VI values > 150 (24). Also, Gross and co-workers synthesized a star polymer containing a ethyl glucoside core and pCL and poly(lactide) arms via a chemo-enzymatic approach (43). 

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