1. Pharmacology – II PHL-322 CNS Pharmacology
Lecture 1: DRUGS USED IN DEPRESSION
(Antidepressants)
By: Abdulaziz Bin Saeedan Ph.D. Assistant Professor Department of Pharmacology E mail:

2. Content Layout with List
OVERVIEW: DEPRESSION AND ANTIDEPRESSANTS
MECHANISM OF ANTIDEPRESSANTS
SELECTIVE SEROTONIN REUPTAKE INHIBITORS
SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS
SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs)
SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)
ATYPICAL ANTIDEPRESSANTS
TRICYCLIC ANTIDEPRESSANTS (TCAs)
MAO (Monoamine oxidase) INHIBITORS
TREATMENT OF MANIA AND BIPOLAR DISORDER

3. I. OVERVIEW: DEPRESSION AND ANTIDEPRESSANTS
The symptoms of depression are feelings of sadness and hopelessness, as well as the inability to experience pleasure in usual activities, changes in sleep patterns and appetite, loss of energy, and suicidal thoughts.
Mania is characterized by the opposite behavior: enthusiasm, anger, rapid thought and speech patterns, extreme self-confidence, and impaired judgment.
Classes of Antidepressants:
SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs)
SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)
ATYPICAL ANTIDEPRESSANTS
TRICYCLIC ANTIDEPRESSANTS (TCAs)
MAO (Monoamine oxidase) INHIBITORS

4. II. MECHANISM OF ANTIDEPRESSANTS
Antidepressant drugs potentiate, either directly or indirectly, the actions of norepinephrine and/or serotonin (5-HT) in the brain.
Biogenic amine theory: depression is due to a deficiency of monoamines, such as norepinephrine and serotonin, at certain key sites in the brain.
Conversely, the theory proposes that mania is caused by an overproduction of these neurotransmitters.
However, the biogenic amine theory of depression and mania is overly simplistic. 4

5. III. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI’s)
SSRI’s specifically inhibit serotonin reuptake, having 300- to 3000-fold greater selectivity for the serotonin transporter, as compared to the norepinephrine transporter.
SSRIs have little blocking activity at muscarinic, α-adrenergic, and histaminic H1 receptors. Therefore, common side effects associated with TCAs, such as orthostatic hypotension, sedation, dry mouth, and blurred vision, are not commonly seen with the SSRIs.
Because they have different adverse effects and are relatively safe even in overdose, the SSRIs have largely replaced TCAs and monoamine oxidase inhibitors (MAOIs) as the drugs of choice in treating depression.
The SSRIs include fluoxetine (the prototypic drug), citalopram, escitalopram (Isomer of citalopram), fluvoxamine, paroxetine, and sertraline. 5

6. III. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI’s) [ Continued… ]
A. Actions
The SSRIs block the reuptake of serotonin, leading to increased concentrations of the neurotransmitter in the synaptic cleft.
B. Therapeutic uses
The primary indication for SSRIs is depression, for which they are as effective as the TCAs.
C. Pharmacokinetics
All of the SSRIs are well absorbed after oral administration.
Food has little effect on absorption (except with sertraline, for which food increases its absorption).
Metabolism by cytochrome P450 (CYP450)-dependent enzymes and glucuronide or sulfate conjugation occur extensively.
Dosages of the SSRIs should be reduced in patients with hepatic impairment. 6

7. III. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI’s) [ Continued… ]
D. Adverse effects
Although the SSRIs are considered to have fewer and less severe adverse effects than the TCAs and MAOIs, the SSRIs are not without adverse effects.
1. Sleep disturbances
Paroxetine and fluvoxamine are generally more sedating than activating, fluoxetine or sertraline are more activating.
2. Sexual dysfunction.
3. Weight gain
Fluoxetine and sertraline have the lowest incidence of weight gain during long-term treatment, paroxetine and citalopram are higher. 7

8. III. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI’s) [ Continued… ]
4. Overdose:
Overdose with SSRIs does not usually cause cardiac arrhythmias, with the exception of citalopram (The TCAs have a significant risk for arrhythmias in overdose)
All SSRIs have the potential to cause serotonin syndrome, especially when used in the presence of a MAOI or other highly serotonergic drug. Serotonin syndrome may include the symptoms of hyperthermia, muscle rigidity, sweating, myoclonus (clonic muscle twitching), and changes in mental status and vital signs.
5. Discontinuation syndrome:
All of the SSRIs have the potential to cause a discontinuation syndrome after their abrupt withdrawal, particularly the agents with shorter half-lives and inactive metabolites such as such as paroxetine, sertraline, and fluvoxamine. 8

9. IV. SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)
Venlafaxine, desvenlafaxine, levomilnacipran, and duloxetine inhibit the reuptake of both serotonin and norepinephrine.
Depression is often accompanied by chronic painful symptoms, such as backache and muscle aches, against which SSRIs are also relatively ineffective. This pain is, in part, modulated by serotonin and norepinephrine pathways in the central nervous system (CNS).
Both SNRIs and the TCAs, with their dual inhibition of both serotonin and norepinephrine reuptake, are sometimes effective in relieving pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, and low back pain. 9

10. Venlafaxine and desvenlafaxine
IV. SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) [ Continued… ]
Venlafaxine and desvenlafaxine
Venlafaxine is a potent inhibitor of serotonin reuptake and, at medium to higher doses, is an inhibitor of norepinephrine reuptake.
Desvenlafaxine is the active, demethylated metabolite of venlafaxine. The clinical activity and adverse effect profile of desvenlafaxine are similar to that of venlafaxine.
B. Duloxetine
Duloxetine inhibits serotonin and norepinephrine reuptake at all doses. It is extensively metabolized in the liver to inactive metabolites and should be avoided in patients with liver dysfunction.
C. Levomilnacipran
Levomilnacipran is an enantiomer of milnacipran 10

11. V. ATYPICAL ANTIDEPRESSANTS
The atypical antidepressants are a mixed group of agents that have actions at several different sites.
This group includes bupropion, mirtazapine, nefazodone, trazodone, vilazodone, and vortioxetine.
A. Bupropion
Bupropion is a weak dopamine and norepinephrine reuptake inhibitor that is used to alleviate the symptoms of depression.
Bupropion is also useful for decreasing cravings and attenuating withdrawal symptoms of nicotine in patients trying to quit smoking.
B. Mirtazapine
Mirtazapine enhances serotonin and norepinephrine neurotransmission by serving as an antagonist at presynaptic α2 receptors. Additionally, some of the antidepressant activity may be related to antagonism at 5-HT2 and 5-HT3 receptors. 11

12. VI. TRICYCLIC ANTIDEPRESSANTS (TCA’s)
The TCAs block norepinephrine and serotonin reuptake into the presynaptic neuron. The TCAs include the tertiary amines
The TCAs include the tertiary amines – imipramine (the prototype drug), amitriptyline, clomipramine, doxepin, and trimipramine,
and the secondary amines
desipramine and nortriptyline (the N-demethylated metabolites of imipramine and amitriptyline, respectively) and protriptyline.
Maprotiline and amoxapine are related “tetracyclic” antidepressant agents and are commonly included in the general class of TCAs. 12

13. VI. TRICYCLIC ANTIDEPRESSANTS (TCAs) [ Continued… ]
Mechanism of action
Inhibition of neurotransmitter reuptake:
TCAs and amoxapine are potent inhibitors of the neuronal reuptake of norepinephrine and serotonin into presynaptic nerve terminals.
Maprotiline and desipramine are relatively selective inhibitors of norepinephrine reuptake.
2. Blocking of receptors:
TCAs also block serotonergic, α-adrenergic, histaminic, and muscarinic receptors. It is not known if any of these actions produce the therapeutic benefit of the TCAs. However, actions at these receptors are likely responsible for many of their adverse effects.
Amoxapine also blocks 5-HT2 and dopamine D2 receptors. 13

14. VI. TRICYCLIC ANTIDEPRESSANTS (TCAs) [ Continued… ]
B. Actions
The TCAs elevate mood, improve mental alertness, increase physical activity, and reduce morbid preoccupation in 50% to 70% of individuals with major depression.
C. Therapeutic uses
The TCAs are effective in treating moderate to severe depression. Some patients with panic disorder also respond to TCAs.
Imipramine has been used to control bed-wetting in children older than 6 years
of age; however, it has largely been replaced by desmopressin and nonpharmacologic treatments (enuresis alarms).
The TCAs, particularly amitriptyline, have been used to help prevent migraine headache and treat chronic pain syndromes
Low doses of TCAs, especially doxepin, can be used to treat insomnia. 14

15. VI. TRICYCLIC ANTIDEPRESSANTS (TCAs) [ Continued… ]
D. Pharmacokinetics
TCAs are well absorbed upon oral administration. These drugs are metabolized by the hepatic microsomal system and conjugated with glucuronic acid. Ultimately, the TCAs are excreted as inactive metabolites via the kidney.
E. Adverse effects
Blockade of muscarinic receptors leads to blurred vision, xerostomia (dry mouth), urinary retention, sinus tachycardia, constipation, and aggravation of angle- closure glaucoma 15

16. VII. MONOAMINE OXIDASE INHIBITORS (MAOI’s)
Monoamine oxidase (MAO) is a mitochondrial enzyme found in nerve and other tissues, such as the gut and liver. In the neuron, MAO functions as a “safety valve” to oxidatively deaminate and inactivate any excess neurotransmitters (for example, norepinephrine, dopamine, and serotonin) that may leak out of synaptic vesicles when the neuron is at rest.
The MAOIs may irreversibly or reversibly inactivate the enzyme, permitting neurotransmitters to escape degradation and, therefore, to accumulate within the presynaptic neuron and leak into the synaptic space.
The four MAOIs currently available for treatment of depression include phenelzine, tranylcypromine, isocarboxazid, and selegiline.
Use of MAOIs is limited due to the complicated dietary restrictions required while taking these agents. 16

17. VII. MONOAMINE OXIDASE INHIBITORS (MAOI’s) [ Continued… ]
Mechanism of action
Most MAOIs, such as phenelzine, form stable complexes with the enzyme, causing irreversible inactivation.
These drugs inhibit not only MAO in the brain but also MAO in the liver and gut that catalyzes oxidative deamination of drugs and potentially toxic substances, such as tyramine, which is found in certain foods.
The MAOIs, therefore, show a
high incidence of drug–drug and drug–food interactions. 17

18. VII. MONOAMINE OXIDASE INHIBITORS (MAOI’s) [ Continued… ]
B. Actions
Although MAO is fully inhibited after several days of treatment, the antidepressant action of the MAOIs, like that of the SSRIs, SNRIs, and TCAs, is delayed several weeks.
C. Therapeutic uses
The MAOIs are indicated for depressed patients who are unresponsive or allergic to TCAs and SSRIs or who experience strong anxiety.
Because of their risk for drug–drug and drug–food interactions, the MAOIs are considered last-line agents in many treatment settings.
D. Pharmacokinetics
These drugs are well absorbed after oral administration. Enzyme regeneration, when irreversibly inactivated, varies, but it usually occurs several weeks after termination of the drug. MAOIs are hepatically metabolized and excreted rapidly in urine. 18

19. VII. MONOAMINE OXIDASE INHIBITORS (MAOI’s) [ Continued… ]
E. Adverse effects
Severe and often unpredictable side effects, due to drug–food and drug–drug interactions, limit the widespread use of MAOIs.
For example, tyramine, which is contained in foods, such as aged cheeses and meats, chicken liver, pickled or smoked fish, and red wines, is normally inactivated by MAO in the gut. Individuals receiving a MAOI are unable to degrade tyramine obtained from the diet. Tyramine causes the release of large amounts of stored catecholamines from nerve terminals, resulting in a hypertensive crisis, with signs and symptoms such as occipital headache, stiff neck, tachycardia, nausea, hypertension, cardiac arrhythmias, seizures, and, possibly, stroke.
Patients must, therefore, be educated to avoid tyramine-containing foods. 19

20. VIII. TREATMENT OF MANIA AND BIPOLAR DISORDER
The treatment of bipolar disorder has increased in recent years, due to increased recognition of the disorder and also an increase in the number of available medications for the treatment of mania.
A. Lithium
Lithium salts are used acutely and prophylactically for managing bipolar patients.
Although many cellular processes are altered by treatment with lithium salts, the mode of action is unknown.
The therapeutic index of lithium is extremely low, and lithium salts can be toxic. Common adverse effects may include headache, dry mouth, polydipsia, polyuria, polyphagia, GI distress (give lithium with food), dizziness, fatigue, dermatologic reactions, and sedation. 20

21. VIII. TREATMENT OF MANIA AND BIPOLAR DISORDER [ Continued… ]
B. Other drugs
Several antiepileptic drugs, including carbamazepine, valproic acid, and lamotrigine, have been approved as mood stabilizers for bipolar disorder.
Other agents that may improve manic symptoms include the older (chlorpromazine and haloperidol) and newer antipsychotics. 21

22. Thank You Any Questions Animated open book effect (Difficult)
Tip: You will need to use drawing guides and the ruler to position the objects on this slide.
To display the drawing guides and the ruler, do the following:
On the Home tab, in the Slides group, click Layout, and then click Blank.
Right-click the slide background area, and then click Grid and Guides. In the Grid and Guides dialog box, under Guide settings, select Display drawing guides on screen. (Note: One horizontal and one vertical guide will display on the slide at 0.00, the default position. The spine of the book will be aligned to the vertical drawing guide.)
On the View tab, in the Show/Hide group, select Ruler.
To reproduce the first shape in the Book cover group on this slide, do the following:
On the Home tab, in the Drawing group, click Shapes, and then under Rectangles click Rounded Rectangle (second option from the left). On the slide, drag to draw a rounded rectangle.
Select the rounded rectangle. Under Drawing Tools, on the Format tab, in the Size group, do the following:
In the Shape Height box, enter 4.5”.
In the Shape Width box, enter 3.33”.
On the rounded rectangle, drag the yellow diamond adjustment handle to the left to decrease the amount of rounding on the corners.
On the Home tab, in the bottom right corner of the Drawing group, click the Format Shape dialog box launcher. In the Format Shape dialog box, click Fill in the left pane, select Gradient fill in the Fill pane, and then do the following:
In the Type list, select Linear.
Click the button next to Direction, and then click Linear Right (first row, fourth option from the left).
In the Angle box, enter 0°.
Under Gradient stops, click Add gradient stops or Remove gradient stops until two stops appear in the slider.
Also under Gradient stops, customize the gradient stops that you added as follows:
Select the first stop in the slider, and then do the following:
In the Position box, enter 0%.
Click the button next to Color, and then under Theme Colors, click Red, Accent 2, Darker 50% (sixth row, sixth option from the left).
Select the second stop in the slider, and then do the following:
In the Position box, enter 100%.
Click the button next to Color, and then under Theme Colors, click Red, Accent 2, Darker 25% (fifth row, sixth option from the left).
Also in the Format Shape dialog box, click Line Color in the left pane. In the Line Color pane, select No line.
Also in the Format Shape dialog box, click 3-D Format in the left pane, and then in the 3-D Format pane, do the following:
Under Bevel, click the button next to Top, and then under Bevel click Circle (first row, first option from the left). Next to Top, in the Width box, enter 4 pt, and in the Height box, enter 4 pt.
Under Surface, click the button next to Material, and then under Standard click Warm Matte (second option from the left).
Also under Surface, click the button next to Lighting, and then under Neutral, click Three Point (first row, first option from the left).
On the slide, drag the rounded rectangle until the left edge is against the vertical drawing guide.
On the Home tab, in the Drawing group, click Arrange, point to Align, and then do the following:
Click Align to Slide.
Click Align Middle.
To reproduce the second shape in the Book cover group on this slide, do the following:
On the Home tab, in the Clipboard group, click the arrow under Paste, and then click Duplicate.
On the slide, drag the duplicate rectangle until the left edge is against the vertical drawing guide.
Under Drawing Tools, on the Format tab, in the Size group, in the Shape Width box, enter 0.73”.
Click the button next to Direction, and then click Linear Left (first row, fifth option from the left).
In the Angle box, enter 180°.
Click the button next to Color, and then under Theme Colors, click Black, Text 1 (first row, second option from the left).
In the Transparency box, enter 50%.
In the Transparency box, enter 100%.
Also in the Format Shape dialog box, click 3-D Format in the left pane. In the 3-D Format pane, under Bevel, click the button next to Top, and then under No Bevel, click None.
To reproduce the third shape (first small rectangle on the book spine) in the Book cover group on this slide, do the following:
Select the first, larger rectangle on the slide. On the Home tab, in the Clipboard group, click the arrow to the right of Copy, and then click Duplicate.
Select the third, duplicate rectangle. Under Drawing tools, on the Format tab, in the Size group, do the following:
In the Shape Height box, enter 0.08”.
In the Shape Width box, enter 0.73”.
Click the button next to Direction, and then click Linear Diagonal (first row, third option from the left).
In the Angle box, enter 135°.
Under Bevel, next to Top, in the Width box, enter 3 pt, and in the Height box, enter 3 pt.
Under Surface, click the button next to Lighting, and then under Neutral click Soft (first row, third option from the left).
To reproduce the rest of the shapes (other small rectangles on the book spine) in the Book cover group on this slide, do the following:
Select the third, smaller rectangle.
On the Home tab, in the Clipboard group, click the arrow to the right of Copy, and then click Duplicate. Repeat this process for a total of four thin, rounded rectangles.
To position the four thin, rounded rectangles on the book spine, do the following:
Drag the first rectangle 1.75” above the horizontal drawing guide, with the left edge touching the vertical drawing guide.
Drag the second rectangle 0.75” above the horizontal drawing guide, with the left edge touching the vertical drawing guide.
Drag the third rectangle 0.75” below the horizontal drawing guide, with the left edge touching the vertical drawing guide.
Drag the fourth rectangle 1.75” below the horizontal drawing guide, with the left edge touching the vertical drawing guide.
On the Home tab, in the Editing group, click Select, and then click Select All.
On the Home tab, in the Drawing group, click Arrange, and then click Group.
On the Home tab, in the Editing group, click Select, and then click Selection Pane.
On the Selection and Visibility pane, double-click the group to edit the name, and then enter Book cover.
To reproduce the first shape in the Inside-left pages group on this slide, do the following:
Under Drawing Tools, on the Format tab, in the Size group, do the following:
Click the button next to Color, and then under Theme Colors, click Red Accent 2, Darker 25% (fifth row, sixth option from the left).
Also in the Format Shape dialog box, click Line Color in the left pane, and then in the Line Color pane, select No line.
On the slide, drag the rectangle until the right edge is against the vertical guideline.
On the Home, tab, in the Drawing group, click Arrange, point to Align, and then do the following:
To reproduce the second shape in the Inside-left pages group on this slide, do the following:
On the Home tab, in the Drawing group, click Shapes, and then under Rectangles click Rectangle (first option from the left). On the slide, drag to draw a rectangle.
In the Shape Height box, enter 4.33”.
In the Shape Width box, enter 3.15”.
Under Gradient stops, click Add gradient stops or Remove gradient stops until five stops appear in the slider.
Click the button next to Color, and then under Theme Colors, click White, Background 1, Darker 35% (fifth row, first option from the left).
In the Position box, enter 5%.
Click the button next to Color, and then under Theme Colors, click White, Background 1 (first row, first option from the left).
Select the third stop in the slider, and then do the following:
In the Position box, enter 18%.
Click the button next to Color, and then under Theme Colors, click White, Background 1, Darker 5% (second row, first option from the left).
Select the fourth stop in the slider, and then do the following:
In the Position box, enter 38%.
Select the fifth stop in the slider, and then do the following:
In the Position box, enter 93%.
Click the button next to Color, and then under Theme Color,s click White, Background 1 (first row, first option from the left).
Also in the Format Shape dialog box, click Shadow in the left pane. In the Shadow pane, click the button next to Presets, under Outer click Offset Right (second row, first option from the left), and then do the following:
In the Transparency box, enter 60%.
In the Size box, enter 100%.
In the Blur box, enter 4 pt.
In the Distance box, enter 3 pt.
On the slide, drag the rectangle until the right edge touches the vertical drawing guide.
Press and hold CTRL, and then in the Selection and Visibility task pane, select the rectangle and the rounded rectangle to the left of the vertical drawing guide.
In the Selection and Visibility task pane, double-click the new group to edit the name, and then enter Inside-left pages.
To reproduce the first shape in the Inside-right pages with text group, do the following:
In the Selection and Visibility task pane, select the Inside-left pages group.
On the Home tab, in the Clipboard group, click the arrow to the right of Copy, and then click Duplicate.
On the Home tab, in the Drawing group, click Arrange, point to Rotate, and then click More Rotation Options. In the Size and Position dialog box, on the Size tab, under Size and rotation, in the Rotation box, enter 180°.
In the Selection and Visibility task pane, double-click the new group to edit the name, and then enter Inside-right pages.
On the slide, drag the rectangle until the left edge is against the vertical drawing guide.
To reproduce the text effects in the Inside-right pages with text group, do the following:
On the Insert tab, in the Text group, click Text Box, and then on the slide, drag to draw a text box.
Enter text in the text box, and then select the text. (Note: To reproduce the example above, enter Introduction.) On the Home tab, in the Font group, do the following:
In the Font list, select Vivaldi.
In the Font Size list, select 18.
On the Home tab, in the Paragraph group, click Center to center the text in the text box.
On the slide, drag the text box until the left edge of the text is 1” to the right of the vertical drawing guide and the bottom edge of the text is 0.5” above the horizontal drawing guide.
To reproduce the page edges in the Inside-right pages with text group, do the following:
On the Home tab, in the Drawing group, click Shapes, and then under Lines click Line (first option from the left).
On the slide, press and hold SHIFT, and then drag to draw a straight, vertical line.
Select the line. Under Drawing Tools, on the Format tab, in the Size group, in the Shape Width box, enter 4.32”.
Under Drawing Tools, on the Format tab, in the Shape Styles group, click the arrow next to Shape Outline, and then under Theme Colors, click White, Background 1, Darker 15% (third row, first option from the left).
On the Home tab, in the Clipboard group, click the arrow to the right of Copy, and then click Duplicate. Repeat this process for a total of six lines.
On the slide, drag the six lines until they are bunched together in a dense group, no wider than 0.5”.
In the Selection and Visibility task pane, press and hold CTRL, and then select all six straight connectors (lines).
Point to Align, and then click Align Selected Objects.
Point to Align, and then click Distribute Horizontally.
Point to Align, and then click Align Middle.
Click Group.
On the slide, drag the group of lines until the right edge of the group of lines is touching the right edge of the white rectangle to the right of the vertical drawing guide.
In the Selection and Visibility task pane, press and hold CTRL, and then select the group of lines, the text box, and the Inside-right pages group.
On the Home tab, in the Drawing group, click the arrow under Arrange, and then click Group.
In the Selection and Visibility task pane, double-click the new group to edit the name, and then enter Inside-right pages with text.
To reproduce the animation effects on this slide, do the following:
In the Selection and Visibility pane, select the Book cover group. On the Home tab, in the Drawing group, click Arrange, and then click Bring to Front.
In the Selection and Visibility pane, select the Inside-left pages group. On the Home tab, in the Drawing group, click Arrange, and then click Bring Forward.
In the Selection and Visibility pane, select the Book cover group. On the Animations tab, in the Advanced Animation group, click Add Animation, point to Exit, and then click More Exit Effects. In the Add Exit Effect dialog box, under Basic, click Wipe.
On the Animations tab, in the Timing group, do the following:
In the Start list, select With Previous.
In the Duration box, enter 1.00 second.
Also on the Animations tab, in the Animation group, click Effect Options, and then click From Right.
In the Selection and Visibility pane, select the Inside-left pages group. On the Animations tab, in the Advanced Animation group, lick Add Animation, point to Entrance, and then click More Entrance Effects. In the Add Entrance Effect dialog box, under Basic, click Wipe.
In the Start list, select After Previous.
In the Duration box, select 1.00 seconds.
To reproduce the background effects on this slide, do the following:
Right-click the slide background area, and then click Format Background. In the Format Background dialog box, click Fill in the left pane, select Gradient fill in the Fill pane, and then do the following:
Click the button next to Direction, and then click Linear Down (first row, second option from the left).
In the Position box, enter 63%.
Click the button next to Color list, and then under Theme Colors, click Black, Text 1, Lighter 50% (second row, second option from the left).