Dopaminergic agonists

More than 40 medications have been investigated but none have shown consistent efficacy for primary cocaine or amphetamine dependence. These medications include dopaminergic agonists, antidepressants, and more recently disulfiram, selegiline, and a cocaine vaccine (see Table 5—2 for summary). Studies have been relatively brief and have focused on abstinence initiation rather than on relapse prevention, but even these modest treatment goals have not been attained. The focus in the discussion that follows is on pharmacotherapies for cocaine dependence, because very few clinical trials have been completed with amphetamine-dependent patients. Furthermore, none of the studies of amphetamine dependence have shown results different from those described for cocaine dependence (Rawson et al. 2002b Srisurapanont et al. 2001). 

Kantak and Miczek 1986). Amphetamine and cocaine, as well as dopaminergic agonists, increase further the already high levels of defensive responses in aggregated rats undergoing withdrawal from opiates, leading in extreme cases to the death of the subjects (Lai et al. 1971 Puri and Lai 1973). 

Iwamoto, E.T. Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat Influence of dopaminergic agonists and antagonists. J Pharmacol Exp Ther 217 451-460, 1981. 

Walsh TJ, Schulz DW, Tilson HA, et al. 1996. Acute exposure to triethyl lead enhances the behavioral effects of dopaminergic agonists Involvement of brain dopamine in organolead neurotoxicity. Brain Res 363 222-229. 

For all agonists, it is advisable to progressively increase the daily dose to reach optimal dose by plateaus. The optimal dose is titrated individually. In combination with levodopa, dopaminergic agonists lower the daily requirements for dopa and, after years of treatment, would prolong the duration of on phases and limit fluctuations in motricity and dyskinesia. Apomorphine is only indicated for patients with on-off swings, either via single-dose subcutaneous injections or a continuous infusion. 

Type B effects are rare but should be recognized. They include oedema of the lower limbs (bromocriptine, amantadine), livedo reticularis (amantadine), diarrhoea (tolcapone, entacapone), paroxysmal hypertension and dysregulation of blood pressure control (selegiline), narcoleptic phenomena (pramipex-ole), and insomnia (all dopaminergic agonists). 

Mechanism of Action A dopaminergic agonist that blocks the uncoating of influenza A virus, preventing penetration into the host and inhibiting M2 protein in the assembly of progeny virions. Amantadine also blocks the reuptake of dopamine into presyn-aptic neurons and causes direct stimulation of postsynaptic receptors. Therapeutic Effect Antiviral and antiparkinsonian activity. 

Dopaminergic agonists such as bromocriptine and apomorphine, which act directly on postsynaptic receptors, do not provoke psychosis-like states in healthy subjects. 

It is a dopaminergic agonist and improves memory, concentration and vigilance in older individuals. 

Figure 9. Specificity of fi-adrenergic and dopaminergic stimulation of cAMP accumulation. Dispersed parathyroid cells were incubated with the indicated fi-adrenergic or dopaminergic agonists either alone (open bars), with 1 pM (—) propranolol (solid bars), or with 10 pM- a-flupenthixol (stippled bars).

ADTN and other dopamine agonists mimicked this effect which was antagonized by a- and B-flupenthixol, the a-isomer being 100 times more potent. In a similar way, dopamine caused a rapid 20-30-fold increase in cellular cAMP in dispersed bovine parathyroid cells. The potency of a series of dopaminergic agonists and antagonists on adenylate cyclase activity paralleled the effects of these ligands on CAMP accumulation and parathormone secretion (16). It was concluded that bovine parathyroid cells possess dopamine sites which are involved in the control of parathormone secretion. 

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