True: Prolonged exposure to agonists causes receptors to both desensitize and down-regulate.

Desensitization occurs first (within minutes) and may be related to receptor phosphorylation.

Down-regulation occurs later (a timeframe of hours) and is due to receptor internalization and degradation, though decreased levels of receptor mRNA are also seen.

The opposite is true in that chronic administration of antagonists results in receptor up-regulation (Cooper et al 2003, p. 81).

False: The binding of antagonists to agonists and the prevention thereby of them reaching receptors is known as chemical antagonism. For example, a chelating agent may be used to counter the effect of heavy metals. It is a rare form of antagonism. Most antagonists bind with the receptor, thus preventing the agonist reaching the receptor (Rang et al 2003, p. 18).

False: The area under the curve (AUC) refers to the area under the plasma concentration–time curve. AUC is lesser if the drug elimination is faster (Anderson & Reid 2002, p. 28; Rang et al 2003, p. 116).

False: In first-order kinetics the rate of absorption or elimination is directly proportional to the amount of drug remaining.

In zero-order kinetics a fixed amount of drug is absorbed or eliminated per minute, independent of the drug concentrations. This is because of rate limiting factors, e.g. in the metabolism of alcohol (Anderson & Reid 2002, p. 27).

False: Second messengers are characteristic of G-protein coupled receptors (Rang et al 2003, p. 33).

True: Therapeutic range is the range of plasma concentrations that yield therapeutic success. The size of therapeutic window, i.e. the therapeutic index (TI), is the ratio of the maximum tolerated concentration to the minimum effective concentration. In practice, we compare the dose at which 50% of the people have the desired outcome (effective dose 50 or ED₅₀) with the dose at which 50% have side-effects (toxic dose 50 or TD₅₀). TI is the ratio of the TD₅₀ to the ED₅₀. The closer TD₅₀ is to ED₅₀, the narrower the margin of safety and the greater the risk of side-effects (Bennett & Brown 2003, p. 94; King 2004, p. 72).

False: The binding of two acetylcholine molecules at the two alpha subunits of a nicotinic receptor-channel results in the opening of that channel (Kandel et al 2000, p. 200).

False: Albumin has a high affinity for acidic drugs, although a low capacity for binding acidic drugs. Acidic drugs bind in small quantities, but they do bind strongly and are hard to displace. This is particularly relevant in renal failure, when the concentration of acidic drugs such as phenytoin may be affected. The unbound percentage of phenytoin may increase from the usual 9% to 19% in renal disease (Bennett & Brown 2003, p. 111).

True: D-Cycloserine is a partial agonist at the NMDA glutamate receptor. It enhances the extinction of conditioned fear in rodents. It is being investigated in the treatment of phobias.

True: There are three main dopamine pathways:

False: Although often used in concert with dopamine antagonists in the treatment of acute mania, lithium does not have any effect on dopamine levels, dopamine turnover or dopamine receptor mediated behaviour (Anderson & Reid 2002, p. 80).

False: Bromocriptine is a dopamine agonist. It is used to treat Parkinsonism, extrapyramidal syndromes, hyperprolactinaemia, galactorrhoea and neuroleptic malignant syndrome (Sadock & Sadock 2005, p. 2999).

False: The dopamine receptors belong to two families. The ‘D₁ like’ include the D₁ and D₅ receptors, which are positively coupled to cAMP. The ‘D₂ like’ include the D₂, D₃ and D₄ receptors, which inhibit cAMP (Anderson & Reid 2002, p. 12).

True: The gate theory of pain suggests that pain results from the balance of activity in nociceptive and non-nociceptive afferents. Morphine produces analgesia partly by activating descending inhibitory pathways. Such pathways may also be activated by endogenous opioid peptides such as endorphins (Kandel et al 2000, p. 483).

False: Glutamate is an NMDA agonist. Glutamate is the major excitatory transmitter in the brain and spinal cord. The glutamate receptors include: the ionotropic receptors that directly gate channels and the metabotropic receptors that indirectly gate channels through second messengers. The subtypes of ionotropic glutamate receptors are AMPA, kainate and NMDA, named according to the agonists that activate them. The action of glutamate on the ionotropic receptors is always excitatory. The activation of metabotropic receptors can produce either excitation or inhibition (Kandel et al 2000, p. 212).

False: Melatonin is a hormone secreted by the pineal gland during darkness. It is thought to play a role in the sleep–wake cycle, and hence, used to treat insomnia and jet-lag. Prolonged use may lead to dependence. It is generally considered to have minimal side-effects (Bennett & Brown 2003, p. 404; King 2004, p. 438).

True: The cholinergic receptors are subdivided into nicotinic and muscarinic. The nicotinic receptors are directly coupled to cation channels and are involved in fast excitatory transmission (Anderson & Reid 2002, p. 22).

True: Clinical and pre-clinical evidence show the cognitive enhancing properties of nicotine (Rang et al 2003, p. 599).

True: Nicotinic receptors are ligand-gated ionotropic channels. Their activation leads to a rapid transient increase in membrane permeability to either cations (especially sodium and calcium) or anions (mainly chloride). They are excitatory. They are blocked by curare. In contrast, muscarinic receptors are G-protein linked, can be excitatory or inhibitory and are blocked by atropine, scopolamine and other anticholinergics (Cookson et al 2002, p. 66; Kandel et al 2000, p. 185; Stahl 2000, p. 468).

False: Administration of noradrenaline reuptake inhibitors leads to increased levels of noradrenaline, and, as a consequence, increased stimulation of presynaptic α₂-receptors. However, this increased stimulation then leads to down-regulation of presynaptic α₂-receptors, leading to reduced sensitivity (Cookson et al 2002, p. 267).

True: The QT interval represents the time between the onset of electrical depolarization and the end of depolarization of the ventricles. Prolongation of the QT interval increases the vulnerability of the myocardium during which ventricular arrhythmias may be precipitated. The length of the QT interval is influenced by the heart rate. Hence, a rate correction is required to interpret its length. QTc is calculated using Bazett’s formula (QT/vRR interval) (King 2004, p. 581).

False: There are seven distinct types of 5-HT receptors: 5-HT₁, 5-HT₂, 5-HT₃, 5-HT₄, 5-HT₅, 5-HT₆, and 5-HT₇. The 5-HT₁ family contains receptors that are negatively coupled to adenylate cyclase (5-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_1E, 5-HT_1F). 5-HT_1C receptors have been reclassified as 5-HT_2C (King 2004, p. 26).

True: There are 14 different serotonin receptors, belonging to 7 groups.

The 5-HT₁ group of receptors (5-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_1E, 5-HT_1F) are inhibitory and are negatively coupled to cAMP. The 5-HT_1C receptor has been reclassified as 5-HT_2C.

5-HT₂ receptors (5-HT_2A, 5-HT_2B, 5-HT_2C) are excitatory. They act through the phospholipase C/inositol phosphate pathway.

The 5-HT₃ receptor is a non-selective cation channel receptor which is permeable to both sodium and potassium ions. Because both calcium and magnesium ions can modulate its activity, it resembles the glutamate NMDA receptor.

5-HT₄, 5-HT₅, 5-HT₆, and 5-HT₇ are excitatory. They act through the phospholipase C/inositol phosphate pathway.

Thus, all serotonin receptors are G-protein coupled (metabotropic), except 5-HT₃ which is a ligand-gated ion channel (ionotropic) (Anderson & Reid 2002, p. 18; Cooper et al 2003, p. 295; King 2004, p. 26; Rang et al 2003, p. 481).

True: The 5-HT₃ receptor is a ligand-gated ion channel receptor (ionotropic receptor). It is a non-selective cation channel receptor permeable to both sodium and potassium ions. Both calcium and magnesium ions can modulate its activity, and thus it resembles the glutamate NMDA receptor (Cooper et al 2003, p. 295; King 2004, p. 26).

False: Substance P is a pain neurotransmitter. Administration of substance P in animals elicits behavioural and cardiovascular effects resembling stress response. Plasma levels of substance P are elevated in depression. Substance P receptor antagonists improve depression, anxiety and emesis, but surprisingly not pain (Sadock & Sadock 2005, pp. 83, 135).