A New Experimental Method for Evaluating Drugs in the Nasal Cavity

Salem, Harry; Clemente, Emmett

doi:10.1001/archotol.1972.00770090802005

Cited by 20 publications

(8 citation statements)

References 18 publications

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“…Antihistamines may prevent the action of histamine on the nasal vascular bed (Jackson, 1970;Salem & Clemente, 1972;Hiley et al 1978), although Bentley & Jackson (1970) could not demonstrate this effect in the dog. Antihistamines have a wide spectrum of pharmacological activity, including sedative, anticholinergic and vasoconstrictive actions (Goodman & Gilman, 1980).…”

Section: Nasal Airway Resistancementioning

confidence: 99%

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Control of nasal vasculature and airflow resistance in the dog.

Lung¹,

Phipps²,

Wang³

et al. 1984

The Journal of Physiology

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SUMMARY1. Nasal vascular and airflow resistances have been measured in dogs, simultaneously on both sides separately.2. Vascular resistance was measured either by constant flow perfusion of the terminal branch of the maxillary artery (which supplies, via the sphenopalatine artery, the nasal septum, most of the turbinates and the nasal sinuses) or by measuring blood flow through this artery, maintained by the dog's own blood pressure.3. Airflowresistancewasassessedbyinsertingballoon-tippedendotrachealcatheters into the back of each nasal cavity via the nasopharynx, and measuring transnasal pressure at constant airflow through each side of the nose simultaneously.4. Preliminary experiments indicated that there was 5-10 % collateral anastomosis between the two sides.5. Close-arterial injection of drugs showed different patterns of response. 6. Adrenaline, phenylephrine, chlorpheniramine and low doses of prostaglandin F2a increased vascular resistance and lowered airway resistance.7. Salbutamol, methacholine and histamine lowered vascular resistance and increased airway resistance.8. Dobutamine decreased airway resistance with a small increase in vascular resistance.9. Prostaglandins E1, E2 and F2a (high dose) decreased both vascular and airway resistances.10. Substance P, eledoisin-related peptide and vasoactive intestinal polypeptide lowered vascular resistance with little change in airway resistance.11. The results are interpreted in terms of possible drug actions on precapillary resistance vessels, sinusoids and venules, and arteriovenous anastomoses. It is concluded that nasal airway resistance cannot be correlated with vascular resistance or blood flow, since the latter has a complex and ill-defined relationship with nasal vascular blood volume. M. A. LUNG AND OTHERS

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Section: Nasal Airway Resistancementioning

confidence: 99%

“…Histamine decreases nasal patency and increases nasal airway resistance (Jackson, 1970;Salem & Clemente, 1972: Hiley et al 1978Matson et al 1978), and it relaxes nasal mucosal strips (Jackson, 1979). It increases nasal blood flow in man (Bende, Elner & Ohlin, 1983).…”

Section: Nasal Airway Resistancementioning

confidence: 99%

Control of nasal vasculature and airflow resistance in the dog.

Lung¹,

Phipps²,

Wang³

et al. 1984

The Journal of Physiology

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“…x-Adrenoceptors agonists constrict the microvas- culature of the nasal mucosal cavity in rats (Salem, 1972), cats (Malm, 1974), dogs (Hall & Jackson, 1968;Loux, 1970) and humans (Eccles, 1982). a-Adrenoceptor agonists of the phenylethylamine and imidazoline types are used clinically as nasal decongestants (Empey & Medder, 1981).…”

Section: ; Timmermans and Vanmentioning

confidence: 99%

Characterization of α‐adrenoceptors in the vasculature of the canine nasal mucosa

Berridge

Roach

1986

British J Pharmacology

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1 a-Adrenoceptors present in the vasculature of the nasal mucosa in P-adrenoceptor blocked dogs have been characterized pharmacologically using selective a,-and M2-adrenoceptor agonists and antagonists. 2 In pentobarbitone-anaesthetized dogs, intra-arterial (i.a.) administration of the selective xlagonists cirazoline and phenylephrine, the selective M2-agonist UK-14,304 and the mixed (,/a2-agonists adrenaline, noradrenaline and oxymetazoline produced dose-related nasal vasoconstrictor responses (as measured by decreases in nasal cavity pressure). The rank order of agonist potency was adrenaline > oxymetazoline = UK-14,304 > noradrenaline > cirazoline > phenylephrine.3 The nasal response to cirazoline was inhibited by the selective ml-adrenoceptor antagonist prazosin but not by the new, potent selective M2-adrenoceptor antagonist RX 811059. In contrast, UK-14,304 was inhibited only by RX 811059. Either prazosin or RX 811059 reduced the effect ofthe mixed agonist adrenaline. 4 In spinal dogs, the noradrenaline-evoked fall in nasal cavity pressure was reduced by either prazosin or RX 811059. Prazosin attenuated markedly the nasal vasoconstrictor response to electrical stimulation of postganglionic fibres emerging from the superior cervical ganglion (SNS) whereas RX 811059 was ineffective. Administration of the neuronal re-uptake inhibitor cocaine potentiated the effect of i.a. noradrenaline but reduced marginally the maximal response to SNS. After cocaine, RX 811059 enhanced the effect of SNS and attenuated the response to noradrenaline. Prazosin reduced effectively the responses to both SNS and noradrenaline after cocaine. Pretreatment with the a2-agonist UK-14,304 did not affect the response to noradrenaline in the nasal cavity but evoked a persistent (up to 2 h) reduction in the response to SNS. RX 811059 antagonized the inhibitory effect of UK-14,304. 5These results demonstrate that both postjunctional a,-and a2-adrenoceptors mediating vasoconstriction are present in the canine nasal mucosa. In addition, sympathetic neurones innervating the nasal mucosa are characterized by a very efficient re-uptake process and contain prejunctional a2-adrenoceptors.

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“…The method used was a modification of that of Salem and Clemente (1972). Essentially, passively sensitized male Hartley guinea pigs, weighing 300-651 g, were used.…”

Section: Methodsmentioning

confidence: 99%

Effects of TMK688, a novel anti-allergic drug, on allergic nasal obstruction and exudative responses in sensitized guinea pigs

Maeda

Abe

Ishii

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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TMK688 (1-[[5'-(3"-methoxy-4"-ethoxycarbonyloxyphenyl)-2',4'-pentadien oyl] aminoethyl]-4-diphenylmethoxypiperidine) is being developed as an orally effective antiallergic drug having both 5-lipoxygenase inhibitory activity and anti-histamine activity (Shizawa et al. 1996; Tohda et al. 1997). The efficacy of TMK688 against allergic rhinitis was examined in passively sensitized guinea pigs. TMK688 inhibited the increase in intranasal resistance following antigen challenge at doses of 1 and 3.2 mg/kg p.o. The allergic nasal obstruction was also suppressed by 10 mg/kg i.v. of FPL-55712, a peptide leukotriene receptor antagonist, but not by 3.2 mg/kg i.v. pyrilamine, a histamine H1 receptor antagonist, or by 10 mg/kg p.o. of ketotifen, an anti-allergic drug having anti-histamine activity, suggesting that the nasal obstruction was caused by leukotrienes. Following antigen challenge, the intranasal release of leukotrienes B4 and C4, and histamine increased in passively sensitized guinea pigs. TMK688 tended to suppress the increase in immunoreactive leukotrienes B4 and C4 in the nasal lavage fluid at a dose of 1 mg/kg p.o., and significantly inhibited the increase at 3.2 mg/kg. The brilliant blue dye leakage following antigen challenge from the blood stream into the nasal cavities was significantly inhibited by not only TMK688 and FPL-55712 but also pyrilamine, suggesting that the allergic dye leakage was caused cooperatively by leukotrienes and histamine. However, ketotifen showed no significant suppression of the dye leakage even at 10 mg/kg p.o., although this drug inhibited the histamine-induced dye leakage at far lower doses (0.1 mg/kg p.o. or higher) in unsensitized guinea pigs. Therefore, histamine is not necessarily the major mediator of allergic dye leakage in our experiment. These findings demonstrate that TMK688 may be superior to antihistamines as a therapeutic agent for allergic rhinitis.

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A New Experimental Method for Evaluating Drugs in the Nasal Cavity

Cited by 20 publications

References 18 publications

Control of nasal vasculature and airflow resistance in the dog.

Control of nasal vasculature and airflow resistance in the dog.

Characterization of α‐adrenoceptors in the vasculature of the canine nasal mucosa

Effects of TMK688, a novel anti-allergic drug, on allergic nasal obstruction and exudative responses in sensitized guinea pigs

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