Antihistaminics and Apomorphine-Induced Vomiting

Abstract

The experiments reported were undertaken to investigate pharmacologically certain claims that some antihistaminics are antemetic in man and capable of inhibiting or preventing apomorphine-induced vomiting in animals. Diphenhydramine hydrochloride, diphenhydramine-8-chlorotheophyllinate, and diphenhydramine- 8-bromotheophyllinate, administered to cats in rotation, by mouth, in doses of from 0.5 to 20 mgm. per kgm. body weight 0.5 hr. before subcutaneous injection of 20 to 50 mgm, per kgm. of apomorphine hydrochloride, had no effect upon the vomiting syndrome. Doses of from 0.5 to 40 mgm. Per kgm. of the same three derivatives of diphenhydramine were administered orally to dogs in rotation and at intervals of 0.5, 1,2, and 4 hr. before intramuscular injection of 0.05 mgm. per kgm. of apomorphine hydrochloride, with no effect upon the incidence of vomiting and no effect upon the frequency of vomiting and retching except partial inhibition at convulsant and subconvulsant doses. Similar results were obtained from administration of promethazine hydrochloride orally to dogs in doses of from 0.5 to 40 mgm. per kgm. one hour before intramuscular injection of 0.05 mgm. per kgm. of apomorphine hydrochloride, and the same procedure, substituting methapyrilene hydrochloride and methapyrilene-8-chlorotheophyllinate for promethazine hydrochloride, did not affect the vomiting syndrome whatsoever. The results indicate that in amounts corresponding to usual human therapeutic doses, none of these antihistaminics has any ability to prevent apomorphine-induced emesis in dogs and cats.

Some Pharmacological Properties of Thioproperazine and Their Modification by Anti‐parkinsonian Drugs

“…Dogs treated with thioproperazine and hyoscine showed no response to apomorphine indicating that if the effective antiapomorphine activity of thioproperazine had been decreased this was by a factor of less than two. Hyoscine is not an inhibitor of emesis induced by apomorphine in the dog (Boyd & Cassel, 1957). A very slight effect was obtained with benztropine, but the change in the ED50 was again by a factor of less than two.…”

Role of Catecholamines and the Chemoreceptor Trigger Zone in Reserpine Induced Emesis

“…The role of catecholamines in emesis is far from clear. That the catecholamines may be concerned in emesis is suggested by (1) the very high concentration of these amines in the chemoreceptor trigger-zone (CT-zone) for emesis situated in the area postrema of the medulla oblongata (Vogt, 1954); (2) epinephrine and its precursors have been shown to potentiate the apomorphine induced emesis (Boyd & Cassell, 1957); Forster & Gunther, 1962); (3) epinephrine induces emesis by intracerebroventricular or intravenous routes in cats and dogs (Borison, 1959;Peng, 1963); and (4) the catecholamine depletors afford protection against emesis induced by 5-HTP (Cahen, 1964), apomorphine (Malhotra & Sidhu, 1956;Boyd & Cassell, 1957;Forster & Kunze, 1962) and staphylococcal enterotoxin (Sugiyama, Bergdoll & Wilkerson, 1960). Although these studies may suggest a role of catecholamines in the emetic response, it cannot be stated whether the catecholamines present in the area postrema have a role in exciting the underlying vomiting centre.…”

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“…It is interesting to note that 2-bromolysergic acid diethylamide, which does not share the central action of lysergic acid diethylamide (Rothlin, 1957), is ineffective. Similarly, it fails to block apomorphine-induced emesis in dogs (Dhawan & Gupta, 1960b) which is antagonized by lysergic acid diethylamide (Dhawan & Gupta, 1960a Brand, Harris, Borison & Goodman, 1954Dhawan & Gupta, 1960aHatcher, 1924Boyd & Cassell, 1957Piala, High, Hassert, Burke & Craver, 1959-Eggles ton, 1916Boyd& Cassell, 1957-Dhawan & Gupta, 1960bBoyd and Cassell, 1957+ Koster, 1957+ Boyd, Cassell, Boyd & Miller, 1955+ Hatcher & Weiss, 1923+ Boyd & Cassell, 1957+ Boyd & Cassell, 1957+: Malhotra & Sidhu, 1956Ballinger & Borison, 1957+ Schallek, Heise, Keith & Bagdon, 1959 LACK OF CORRELATION BETWEEN EFFECTS OF DRUGS ON LATENT PERIOD FOR PECKING AND PROTECTION AFFORDED BY THEM + indicates significant increase of latent period/protection; -a significant decrease in latent period; and 0 no effect. However, many agents have influenced the pecking and emetic response to apomorphine in an identical manner (see Table 2).…”