Dopaminergic mechanisms

Trepipam (69) is a sedative agent apparendy acting via dopaminergic mechanisms. It can be synthesized by attack on the less hindered terminus of styrene oxide (66) by 4,5-dimethoxyphe-nethylamine (65) to give 67. Cyclodehydration catalyzed by strong acid then leads to 68 and N-... 

Dopaminergic mechanisms within the ventral striatum (i.e., nucleus accumbens) subserve the ability of amphetamine and methylphenidate in low to moderate doses to increase locomotor activity. In contrast, very low dosages in animals seem to cause hypoactivity presumably by stimulation of autoreceptors, a finding that would be compatible with the clinical impression that methylphenidate might be usefiil in some patients with mania. 

Gwen, F. Baker, H.F. Ridley, R.M. Cross, A.J. and Crow, T.J. Effect of chronic amphetamine administration on central dopaminergic mechanisms in the vervet. Psychopharmacology (Berlin) 74 213-216, 1981. 

Another advantage in studying the striatum, with particular emphasis on dopaminergic mechanisms, is that we may gain some insight into the factor underlying the production, by PCP, of schizophrenic symptoms in humans. 

Opioid effects on memory are consistent in humans and animal models (Braida et al. 1994 Saha et al. 1991). Verbal and visual memory are impaired by morphine one hour after oral administration (Hanks et al. 1995 Kerr et al. 1991). These could be due to direct neuronal effects of opioids, or perhaps through indirect effects on cholinergic transmission. However, in some animal paradigms morphine can enhance memory consolidation through indirect dopaminergic mechanisms (Castellano et al. 1994). 

Clarke PBS (1990) Dopaminergic mechanisms in the locomotor stimulant effects of nicotine, Biochem Pharmacol 40 1427-1432... 

Pharmacology Bupropion is a nonnicotine aid to smoking cessation. The mechanism by which bupropion enhances the ability of patients to abstain from smoking is unknown. However, it is presumed that this action is mediated by noradrenergic or dopaminergic mechanisms. 

Opioids have been shown to increase the release of dopamine in the nucleus accumbens but they also subserve reinforcement in animals by a non-dopaminergic mechanism (Di Chiara 8c North,1992 Koob, 1992). Physiologically the opioid system appears to be largely involved in the con-sumatory rewards of feeding, drinking, sexual and maternal behaviour (Koob, 1992 Di Chiara 8c North, 1992) and certain types of social behaviour (Panksepp, 1981 Bolles 8c Fanselow, 1982). 

The vomiting centre in the hypothalamus receives impulses from the chemo-effector trigger zone (CETZ) and from cortical centres such as emotional, visual and olfactory areas, and from peripheral sources, including the inner ear and gastrointestinal tract. While mainly muscarinic mechanisms operate at the vomiting centre, dopaminergic mechanisms predominate at the CETZ. The CETZ can be stimulated by a multitude of xenobiotics, including medicines. 

Substantial evidence suggests a deficiency of DA in depressive disorders and the involvement of mesolimbic dopaminergic mechanisms in antidepressant... 

Talalaenko AN, Abramets lA, Stakhovskii YuV, et al The role of dopaminergic mechanisms on the brain in various models of anxious states. Neurosci Behav Physiol 24 284-288, 1994... 

Willner P Dopaminergic mechanisms in depression and mania, in Psychopharmacology The Fourth Generation of Progress. Edited by Bloom EE, Kupfer DJ. New York, Raven, 1995, pp 921-931... 

The most common undesirable effect of methyldopa is sedation, particularly at the onset of treatment. With long-term therapy, patients may complain of persistent mental lassitude and impaired mental concentration. Nightmares, mental depression, vertigo, and extrapyramidal signs may occur but are relatively infrequent. Lactation, associated with increased prolactin secretion, can occur both in men and in women treated with methyldopa. This toxicity is probably mediated by inhibition of dopaminergic mechanisms in the hypothalamus. 

The Relationship Between Drug-Induced Reward and Nucleus Accumbens Dopaminergic Mechanisms Some Caveats... 

Cardiovascular Disorders. DA itself is a useful agonist where intravenous therapy is required for immediate effects limited to the periphery (i.e. outside the blood Drain barrier). It has therefore been employed as a pharmacolgical agent in shock - a condition in which there is no disease involving dopaminergic mechanisms, but where the inotropic actions on the heart and vasodilator effects on the kidney can reverse the potentially lethal consequences of profound arterial hypotension, whatever its cause. This subject is discussed in detail elsewhere in this symposium. 

The fresh leaves of the khat shrub (Catha edulis) are chewed by several millions of people in East Africa and the Arabian peninsula for their euphoric and stimulating properties (284). The rather newly discovered alkaloid cathinone [(S)-a-aminopropiophenone] is responsible for the stimulating properties of khat (284). It has been shown that cathinone induces release at physiological catecholamine storage sites in a manner similar to that of amphetamine. Further results suggest that cathinone and amphetamine produce their stimulant effects via the same dopaminergic mechanism (599). The more recently discovered khat constituents merucathinone, merucathine, and pseudomerucathine were found to have only weak dopamine-releasing effects and were therefore considered unlikely to play an important role in the stimulatory actions of khat leaves (414). 

Campbell GA, Eckardt MJ, Weight FF (1985) Dopaminergic mechanisms in subthalamic nucleus of rat analysis using horseradish peroxidase and microiontophoresis. Brain Res 333 261-270. 

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