Anti-emetic activity

Tyers MB, Freeman AJ. Mechanism of the anti-emetic activity of 5-HT3 receptor antagonists. Oncology 1992 49(4) 263-268. 

The existence of chirality in nature is of particular importance in numerous recognition processes, often illustrated by examples detectable by non-spectroscopic methods such as the different orange and lemon odors of R-(+)- and S-(-)-limonene, respectively (Fig. 3) [8]. As such, chiral discrimination is also of considerable consequence in the medical sciences, as often one enantiomer is pharmaceutically active whereas the other may show adverse side effects. A historic example is the anti-emetic activity of one of the enantiomers of thalidomide, while the other can cause fetal damage [9,10]. These considerations highlight the importance of chiral discrimination in the production of biologically active materials, whereas on the other hand, the design of routes to asymmetric synthesis presents an active challenge to synthetic chemists worldwide. 

Prochlorperazine is widely used for its anti-emetic activity and its effectiveness in suppressing dizziness due to labrintine disorder. Oral bioavailability is very low, due to extensive intestinal and hepatic frrstpass metabolism. Furthermore, the oral route is impractical in patients with nausea and vestibular disturbance, who have been demonstrated to have impaired gastric emptying. 

PARP-1 inhibitor with the specificity and in vivo activity to enhance chemotherapy and radiation therapy of human cancer (Calabrese et al, 2004). GR205171 has the most potent anti-emetic activity of any tachykinin NKl receptor antagonist described to date. The compound is orally active in the ferret and dog, long-lasting, and warrants further investigation as a potential broad-spectrum anti-emetic agent (Gardner et al, 1996). 

Digestive system Anti-emetic activity Anti-ulcer activity... 

Cannabis Cannabis sativa) has a long history of medicinal and non-medicinal use and records date back 4,000 years. Naturally occurring cannabis contains a unique class of compounds known as cannabinoids. Over 60 members of this family have been identified but only a few have been well studied. The two best known and most studied cannabinoids are delta-9-tet-rahydrocannabinol (THC) and cannabidiol (CBD) (Fig. 1). These two compoimds show markedly different pharmacological activity. THC is best known for its psycho-activity but also displays analgesic, anti-spasmodic, anti-tremor, anti-inflammatory, and anti-emetic activity. CBD... 

DA antagonists are anti-emetic, elevate plasma prolactin and have major motor and behavioural effects. Thus DA must be involved in the initiation of vomiting, the secretion of prolactin and control of motor and behavioural activity. Its role in emesis and as the prolactin release inhibitory factor have been adequately covered above. Its motor and behavioural function will now be considered. 

Benzimidazole is an important heterocyclic nucleus in the field of medicinal chemistry. The most prominent benzimidazole compound in nature is N-ribosyldimethylbenzimidazole, which serves as an axial ligand for cobalt in vitamin B12. The versatile nature of benzimidazole makes it a highly explored molecule in medicinal chemistry. A number of pharmacological activities are associated with benzimidazole derivatives such as anthelmintic, antiulcer, antipsychotic, proton pump inhibitor, antianxiety, anti-emetic and sedative, vasodilator, anticancer, analgesic, antihistaminic, antifungal, antiviral and antimicrobial. 

Antipsychotic agents are also used for a diversity of other indications like hiccups, Tourette s syndrome, aggressive behavior in children and the elderly and alcohol withdrawal syndrome. Some of them are also used in anesthesia as they can potentiate the sedative, analgesics or anesthetic effects of other agents. Antipsychotics which are mainly active by blocking dopamine activity have also an effect on chemoreceptor trigger zone and may therefore be used as anti-emetics. 

Chiorphenamine is effective in reducing pruritus from opioid drugs and may have synergistic activity with other anti-emetic drugs, although it is not primarily used as an anti-emetic. 

Promethazine has prominent sedative effects as weii as anti-muscarinic and dopamine D2-blocking effects. These make it usefui as an anti-emetic, and it is especially useful for the prevention and treatment of motion sickness. Like other phenothiazines, it has weak al-adrenergic blocking effects and can iower biood pressure if injected rapidly intravenously. Intramuscular injection can be painful. Alimemazine tartrate is a phenothiazine with HI antagonist activity that produces marked sedation. It is used mainiy for its marked relief of pruritus, and is also popular for the premedication of children (dose 2 mg-kg-1). 

Phenothiazines are antipsychotic agents that can be used for their potent anti emetic and sedative properties (see Chapter 29 Antipsychotic Agents Lithium). The anti emetic properties of phenothiazines are mediated through inhibition of dopamine and muscarinic receptors. Sedative properties are due to their antihistamine activity. The agents most commonly used as antiemetics are prochlorperazine, promethazine, and thiethylperazine. 

An example that illustrates the potential of this catalytic C-C bond-forming process to build up key structural subunits of natural products is shown in Scheme 2. The reaction of acetophenone with aldehyde 18 in the presence of 8 mol% catalyst 1 affords the aldol adduct 19 in 70% yield and 93% ee, which is subsequently transformed into 20, a key intermediate of the anticancer agent epothilone A [8b]. Similarly, Scheme 3, the aldol reaction of hydroxyacetylfuran 21 with valeralde-hyde in the presence of 5 mol% catalyst 3 produces syn diol 23 with high efficiency [10d]. Further chemical elaboration of 23 leads to 24, a key intermediate in the synthesis of (+)-boronolide, a folk medicine with emetic and anti-malaria activity. 

Documented effects Preparations from raspberries improve stomach and intestine function, have antiseptic, analgesic, antipyretic, expectorant, anti-inflammatory, and anti-emetic properties, and improve metabolism (Maznev 2004). Extracts of the fruits have antioxidant effects and exhibit antimicrobial properties (Kahkonen et al. 1999 Rauha et al. 2000 Puupponen-Pimia et al. 2001). Components of raspberry leaf extract exhibited relaxant activity in an in vitro gastrointestinal tissue (Rojas-Vera et al. 2002). 

Sulpiride, XXI, has been introduced in Europe and has been reported tg be a clinically important new class f neuroleptic agent ° with strong anti-emetic properties. In mice no emticonvulsant activity was noted. 

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