Apomorphines

Apomorphine has a central depressant effect in man especially if large doses are employed. Even small non-emetic doses of apomorphine may at times be hypnotic, and, when a patient is already depressed, full therapeutic amounts may fail to cause vomiting, and may increase the intensity of the depression. Collapse, coma, and even death have occurred with 

Statements on the possibility of tolerance to the emetic effect of apomorphine are conflicting. Addiction to it seems never to have been reported. Apomorphine has been recommended as a hypnotic in alcoholic delirium. Narcosis caused by morphine seemed to be reenforced Avith apomorphine (1). 

In humans, apomorphine in doses of 5 to 10 mg induces nausea and vomiting within 10 to 15 min. Very often, the nausea passes off immediately after evacuation of the stomach, but when larger quantities have been administered, repeated vomiting and retching may occur. Occasionally, depression and sleep follow emesis after even small doses. 

Very small doses of apomorphine may induce the secondary symptoms without actual vomiting. Thus saliva, perspiration, tears, and other secretions may be augmented by quantities that are too small to act as emetics. 

Apomorphine induces vomiting through changes in the medulla oblongata and not by irritation of the stomach. This is shown by the fact that it acts much more quickly and in smaller doses when administered hypodermically or intramuscularly than when swallowed, as well as by the fact that if the medulla is brushed with apomorphine solution, vomiting follows immediately. Moreover, the 

Emetics, when administered in small doses, act as expectorants and are used in inflammatory conditions of the respiratory tract to increase the bronchial secretion and render it less tenacious. The most commonly used expectorants are ipecac, ammonium chloride, and apomorphine. The last named is administered in doses of 1 mg in the form of an elixir or syrup. Apomorphine injected in subemetic doses of 1 to 2 mg is also used as a sedative in the delirium following anesthesia, in acute alcoholic psychosis, and in patients manifesting severe agitation prior to anesthesia. 

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Apo-4 -carotenal, 8-Apo-8 -carotenaI, 8-Apo-8 -carotenoic acid ethyl ester, 8-Apo-8 -carotenoic acid methyl ester, Apocodeine, Apomorphine see entries in Chapter 6. 

On methylation apomorphine yields apo-i/i-coDEiNE (i/i-apocodeme, anocodeine, apomorphine methyl ether), CigHigOaN. C2H5. OH, crystallising in brilliant plates, m.p. 104-5-106-5°, or 122-5-124-5 dry), — 90° (EtOH), which is also produced when codeine or i/i-codeine is heated with oxalic acid or phosphoric acid. It stands in the same relation to codeine as apomorphine to morphine. 

Comprehensive summaries of the pharmacological information available regarding codeine, apomorphine and thehaine are given in the report already referred to. ... 

The Apomorphine-derived alkaloid PO-3 (129) was isolated as violet needles after crystallization from acetone and ether from Papaver orientale (66MI2), but was not found in the green solutions of autoxidized apomorhine hydrochloride (62M941, 68HCA683) (Scheme 51). No anion was detected by elemental analysis. The pA"a of PO-3 is 3.88 0.02 in 50% ethanol. The IR spectrum displays no carbonyl absorption between 1650 and 1700 cm (69MI2). The UV absorption maxima of PO-3 are in agreement with the formulation of a mesomeric betaine [T-max (EtOH) = 310... 

C 7H,7N03 57-27-2) see Apomorphine Codeine Ethylmorphine Hydromorphone Nalorphine Pholcodine... 

For instance morphine (1) can be detected by the formation of various quinones via apomorphine as intermediate [4, 12, 13]. All morphines with an OH group in the 6-position and a double bond (codeine, ethylmorphine etc.) first undergo an acid-catalyzed rearrangement according to the following scheme [12] ... 

Here the alcoholic hydroxyl is first protonated and then eliminated as water. The allylcarbenium ion (2) is initially stabilized by elimination of the proton at C-14. Then the ether link is opened after protonation of the ring oxygen with the formation of carbenium ion (3), whereby the neighboring C-C bond of the piperidine ring is cleaved with aromatization of the C ring. The carbenium ion (4) formed is stabilized by elimination of a proton and ring closure to apomorphine (5). 

The ortho diphenolic structure of apomorphine makes it a strongly reducing substance hence, in acid medium it forms the blue colored or//io-qulnone (6) with iodine or other oxidizing agent which is in equilibrium with its zwitterionic limiting structure (7) (Pellargi s reaction [14]). 

The Husemann and Erdmann identification reactions for morphine and codeine in the DAB 9 (German Pharmacopoeia) involve the formation of the red-colored ortho-quinone (8) via apomorphine (5) under the influence of nitric acid with the simultaneous nitration of the benzene ring [15]. 

When tested on prolactin release in isolated mammatrophs of bovine anterior pituitary, apomorphine appeared a full agonist (inhibiting release) while antagonism of the inhibition of prolactin release by the neuroleptics showed a potency more similar to that for binding than for blocking cAMP production. Also the inhibition of prolactin... 

DA agonists — bromocriptine, apomorphine and ADTN decrease release. 

Figure 7.5 Rate recording of the dose-dependent inhibitory effects of apomorphine (pg/kg) on the spontaneous activity of a neuron in the medial prefrontal cortex of the halothane anaesthetised rat and its antagonism by haloperidol (HAL, 0.5mg/kg). Time scale is 50 min intervals. Reproduced by permission from Dailey (1992)...

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