Dopamine-receptor agonist interactions

Bromocriptine (Parl el) [Antiparkinsonian Agent/Dopamine Receptor Agonist] Uses Parkin on Dz, hyperprolactinemia, acromegaly, pituitary tumors Action Direct-acting on the striatal dopamine receptors X prolactin secretion Dose Initial, 1.25 mg PO bid titrate to effect, w/ food Caution [B, ] Contra Severe ischemic heart Dz or PVD Disp Tabs, caps SE X BP, Raynaud phenomenon (vasospastic disorder resulting in discoloration of the fmgers/toes), dizziness, N, hallucinations Interactions T Effects W/ erythromycin, fluvoxamine, nefazodone, sympathomimetics, antihypertensives X effects W/ phenothiazines, antipsychotics EMS Monitor BP may cause intolerance to EtOH OD May cause NA, severe hypotension give IV fluids symptomatic and supportive... 

The mechanisms of action of phencyclidine and ketamine are complex (Gorelick Balster, 1995). The drugs are non-competitive antagonists at NMDA receptors, and also bind to associated phencyclidine/sigma opioid receptors. They also have agonist actions at dopamine receptors, complex interactions with both nicotinic and muscarinic acetylcholine receptors and poorly understood interactions with noradrenergic and serotonergic systems. These multiple actions may combine to produce delirium and psychotic reactions. 

Dopamine Dopamine receptor agonist higher doses activate 13 and a adrenoceptors Increases renal blood flow higher doses increase cardiac force and blood pressure Acute decompensated heart failure shock IV only duration a few minutes Toxicity Arrhythmias Interactions Additive with sympathomimetics... 

Wynalda MA, Wienkers LC. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos 1997 25 1211-1214. 

Trade names Apo-Bromocriptine Bromed Cryocriptina Kripton Parilac Parlodel (Novartis) Pravidel Serocryptin Indications Amenorrhea, parkinsonism, infertility Category Dopamine receptor agonist Half-life initial 6-8 hours terminal 50 hours Clinically important, potentially hazardous interactions with erythromycin, lanreotide, pseudoephedrine, sympathomimetics... 

Dopamine, and most of the known dopamine receptor agonists, binds with higher affinity to the dopamine D3 than to the dopamine D2 receptor. Due to the close homology between the dopamine D2 and D3 receptors, especially in the transmembrane domains (-80%), it is difficult to predict dopamine D2 versus dopamine D3 receptor selectivity based on receptor models. Malmberg et al.115 suggested that the observed dopamine D3 receptor selectivity may not be due to a single specific interaction but rather to a small difference in conformation between the dopamine D3 and D2 receptors. 

Bromocriptine (PARLODEL) is the dopamine-receptor agonist against which newer agents are compared. Bromocriptine is a semisynthetic ergot alkaloid that interacts with dopamine receptors to inhibit spontaneous and TRH-induced release of prolactin to a lesser extent, it also activates Dj receptors. Bromocriptine normalizes serum prolactin levels in 70-80% of patients with prolactinomas and decreases tumor size in more than 50fo of patients, including those with macroadenomas. 

Apomorphine is an agonist at both the and D2 receptors. From the pathological viewpoint, a malfunction of the receptors has been implicated in the negative s)nnptoms of schizophrenia but as there is a close interaction between these receptor types it is difficult to conclude whether the changes seen in schizophrenia are attributable to a primary decrease in receptor function or an increase in D2 receptor function. The function of the D5 receptors is unclear these receptors, though widely distributed in the brain, are only present in a relatively low density in comparison to the other dopamine receptor types. 

It belongs to azapirones which is chemically and pharmacologically distinct class. It acts as a partial agonist at serotonin and dopamine receptors and having no hypnotic and sedative action. It does not interact with benzodiazepine receptor or modify GABA-ergic transmission. 

Duarte EP, Oliveira CR, Carvalho AP (1988) Thermodynamic analysis of antagonist and agonist interaction with dopamine receptors. Eur J Pharmacol 147(2) 227-239 Fredholm BB, Ijzerman AP, Jacobson KA, Klotz KN, Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53(4) 527—552... 

All the pharmacological and behavioural effects elicited by dopamine agonists and antagonists in the brain can only be explained if such an interaction occurs at the level of the dopamine receptor (D2 receptor site) the site still remains in search of a function. Bovine parathyroid cells were reported to possess dopamine sites which should be involved in the control of parathormone secretion. However, the very poor pharmacological characterization and the lack of in vivo evidence do not allow to assess the dopaminergic nature of this hormone secretion. Dopamine-sensitive adenylate cyclase is thus not a receptor directly implicated in the dopaminergic neurotransmission it is an enzyme which could have an important role in the control of long term metabolic effects such as the synthesis of neuronal constituents. 

All the data presented above point to the involvement of a putative guanine nucleotide binding protein in the interaction of agonists with the dopamine receptor in the porcine anterior pituitary gland. We, therefore, wanted to obtain more compelling evidence for the interaction of a nucleotide binding... 

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