shorter half-lives and different potencies as inhibitors of specific P450 isoenzymes. Racemic citalopram and (S)-citalopram(escitalopram),the most selective SSRIs of all have achieved very widespread use.Although the SSRIs have not been shown to be more effective overall than prior drugs,they lack many of the toxicities of the tricyclic and heterocyclic antidepressants.Thus,patient acceptance has been high despite their own adverse effects. 5.MAO inhibitors MAO-A (isoform A)is the amine oxidase primarily responsible for norepinephrine,serotonin,and tyramine metabolism.MAO-B is more selective for dopamine.The irreversible inhibitors available in the USA are nonselective and at the doses used block both forms of the enzyme.Irreversible block of MAO,characteristic of the older MAO inhibitors,allows significant accumulation of tyramine and loss of the first-pass metabolism that protects against tyramine in foods(see Adverse Effects). Because they result in replacement of the normal transmitter(norepinephrine)stored in noradrenergic nerve terminal vesicles with a false transmitter (octopamine),they may cause significant hypotension. T 5HT1D.2A VAT VAT MAO-A 02 Ca2+ 5HT1A.1D Figure 30-6 Schematic diagram showing some of the potential sites of action of antidepressant drugs.The primary neuron is shown as releasing a transmitter amine (NT).A modulating neuron may release a second transmitter(NTx),regulating the activity of the primary neuron.The most consistent observed effect of the antidepressants(other than MAO inhibitors)is inhibition of the reuptake transporters (T)for norepinephrine or serotonin.The MAO inhibitors increase the vesicular stores of both NE and 5-HT.Other direct or indirect effects include initial increase in activation of pre-and postsynaptic receptors and subsequent desensitization or down-regulation of transmitter synthesis from an amino acid(AA),receptor numbers, or postreceptor mechanisms.Desensitization resulting from antidepressant use hasshorter half-lives and different potencies as inhibitors of specific P450 isoenzymes. Racemic citalopram and (S)-citalopram (escitalopram), the most selective SSRIs of all, have achieved very widespread use. Although the SSRIs have not been shown to be more effective overall than prior drugs, they lack many of the toxicities of the tricyclic and heterocyclic antidepressants. Thus, patient acceptance has been high despite their own adverse effects. 5. MAO inhibitors MAO-A (isoform A) is the amine oxidase primarily responsible for norepinephrine, serotonin, and tyramine metabolism. MAO-B is more selective for dopamine. The irreversible inhibitors available in the USA are nonselective and at the doses used block both forms of the enzyme. Irreversible block of MAO, characteristic of the older MAO inhibitors, allows significant accumulation of tyramine and loss of the first-pass metabolism that protects against tyramine in foods (see Adverse Effects). Because they result in replacement of the normal transmitter (norepinephrine) stored in noradrenergic nerve terminal vesicles with a false transmitter (octopamine), they may cause significant hypotension. Figure 30-6 Schematic diagram showing some of the potential sites of action of antidepressant drugs. The primary neuron is shown as releasing a transmitter amine (NT). A modulating neuron may release a second transmitter (NTx), regulating the activity of the primary neuron. The most consistent observed effect of the antidepressants (other than MAO inhibitors) is inhibition of the reuptake transporters (T) for norepinephrine or serotonin. The MAO inhibitors increase the vesicular stores of both NE and 5-HT. Other direct or indirect effects include initial increase in activation of pre- and postsynaptic receptors and subsequent desensitization or down-regulation of transmitter synthesis from an amino acid (AA), receptor numbers, or postreceptor mechanisms. Desensitization resulting from antidepressant use has