A2-Adrenergic agonists

A common strategy for treating chronic opiate addiction iavolves the substitution of methadone which can either be provided as maintenance therapy or tapered until abstinence is achieved. Naltrexone and buprenorphine [52485-79-7] have also been used ia this manner. The a2 adrenergic agonist clonidine [4205-90-7] provides some rehef from the symptoms of opiate withdrawal, probably the result of its mimicking the inhibitory effect of opiates on the activity of locus coerukus neurons. 

The imidazoline receptor is a hypothetical receptor for a subgroup of a2 adrenergic agonists, which are characterized by their imidazoline structure (e.g. moxoni-dine). So far, there is no proof of the existence of imidazoline receptors. 

The mRNA expression of PEPT1 varies significantly in response to several chemical factors. The expression of the transporter was upregulated by substrates [89, 90], diet [91, 92], insulin [93], a2-adrenergic agonists [93], and pentazocine [94]. While it has been reported that intestinal transplantation [89, 95], cAMP [96], epidermal growth factor [97], and thyroid hormone [98] inhibited the expression of PEPT1. 

Agents that decrease catecholamines are used for the treatment of mania (e.g, DA antagonists and a2-adrenergic agonists). 

Guanabenz is an a2-adrenergic agonist that exhibits pronounced hypotensive action, and that is associated with a reduction of overall peripheral vascular resistance, decline in frequency of cardiac contractions, and reduced cardiac output. 

Pharmacoepidemiologic data indicate that use of the a2-adrenergic agonists has increased dramatically in the past decade. Swanson et al. (1995) estimated that in... 

Some authors have questioned whether there is sufficient efficacy and safety data to support widespread use of the a2-adrenergic agonists (Cantwell et al., 1997), a position which intensified following the report of several sudden deaths of children who were medicated with clonidine and methylphenidate in combination (Popper, 1995). Although the FDA could not establish a causal link between the medications and these catastrophic outcomes, clearly more research is needed. At the same time, interest at the national level in establishing a more extensive scientific database to support the use of previously off-label prescription patterns, and interest on the part of industry to obtain FDA approval for new indications, suggests that larger... 

This chapter will review the characteristics and regulatory properties of a2 receptors, neuropharmacology of the a2-adrenergic agonists, hypothesized mechanisms by which these medications alter central nervous system (CNS) activity, as well as a variety of issues related to their clinical use, including safety and adverse effects, dosing, and medication interactions. 

Levy, R., Leiphart, J., Dills, C. Analgesic action of acute and chronic intraspinally administered opiate and a2-adrenergic agonists in chronic neuropathic pain, Stereotact. Funct. Neurosurg. 1994, 62, 279-289. 

Asano, T., Dohi, S., lida, H. Antinociceptive action of epidural KATP channel openers via interaction with morphine and an a2-adrenergic agonist in rats, Anesthesia and Analgesia 2000, 90, 1146-1151. 

NE is fundamental in human attention and concentration. It has been demonstrated that idozaxan increase the attention in healthy volunteers (Smith et al., 1992). To contrasy, the administration of a2-adrenergic agonist clonidine results in attention lapses in humans. These clonidine-induced attention difficulties can be reversed by idozaxan (Smith and Nutt 1996). 

Fig. 1. Mechanisms of activation and inactivation of adenylate cyclase. Abbreviations not given in the text or figure are cholera T, Vibrio cholerae toxin IAP, islet activating protein, a Bordetetla pertussis toxin guanine N, guanine nucleotide 0- and a2-agonists, 0- and a2-adrenergic agonists 0. and a, a subunits of Gs and Gj, respectively.

Affective and Mental Disorders. Anxiety and emotional instability can be associated with psychogenic reactions, such as vasovagal syncope, that may appear to be drug related. Medications used to treat these disorders may potentiate the activity of ophthalmic medications. The use of monoamine oxidase inhibitors or tricyclic antidepressants can enhance the systemic effects of topically applied phenylephrine and a2-adrenergic agonists. 

Clonidine is an a2-adrenergic agonist and can therefore be used effectively in portal hypertension at an average dosage of 0.075-0.3 mg/day. 

The injectable formulations of potentiated sulfonamides are suspensions consequently, rapid i.v. administration causes hypotension and collapse. Fatal dysrhythmias are associated with the potentiated sulfonamides administered i.v. concurrently with the a2-adrenergic agonist deto-midine. It is suspected that the potentiated sulfonamide formulation potentiates the cardiac changes produced by detomidine. This adverse reaction has not been reported for the other ci2-adrenergic agonists xylazine and romifidine. 

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