Behavioral effects of histamine H1 antagonists: comparison with other drugs and modification by haloperidol.

Abstract

The behavioral effects of several histamine H1 antagonists were compared in groups of squirrel monkeys trained to respond under fixed-interval schedules involving response-produced shock or termination of a stimulus associated with shock. Low to intermediate doses of the conventional H1 antagonists chlorpheniramine (up to 3.0 mg/kg), diphenhydramine (up to 1.0 or 3.0 mg/kg), pyrilamine (up to 3.0 mg/kg) and tripelennamine (up to 0.3 or 1.0 mg/kg) produced dose-related increases in response rate under all conditions in which they were studied; higher doses either increased responding less or decreased it. In contrast, a wide range of doses of the novel H1 antagonists AHR 11325 (1.0-30.0 mg/kg), astemizole (up to 10.0 mg/kg) and loratadine (up to 17.0 mg/kg) usually had little effect on responding, although decreases in response rate accompanied by emesis were observed after the highest doses in some monkeys. Other H1 antagonists including phenindamine (0.03-17.0 mg/kg), promethazine (0.03-5.6 mg/kg) and terfenadine (0.1-10.0 mg/kg) had different effects in individual subjects (i.e., dose-related increases in response rate in some monkeys and either little change or dose-related decreases in responding in other monkeys). The dopamine uptake inhibitors cocaine (0.01-1.0 mg/kg) and bupropion (0.1-10.0 mg/kg) had behavioral effects similar to those of chlorpheniramine, diphenhydramine, pyrilamine and tripelennamine, whereas the muscarinic antagonist atropine (0.03-1.0 mg/kg), the serotonin 5-hydroxytryptamine/5-hydroxytryptamine antagonist cyproheptadine (0.03-1.0 mg/kg), the norepinephrine uptake inhibitor desmethylimipramine (0.03-3.0 mg/kg) and the benzodiazepine diazepam (0.3-30.0 mg/kg) produced only dose-related decreases in response rate.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: J Bergman, R D Spealman
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 245 Issue 2 Pg. 471-8 (May 1988) ISSN: 0022-3565 [Print] United States
• PMID: 2896793 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Histamine H1 Antagonists
• Propiophenones
• Bupropion
• Cyproheptadine
• Cocaine
• Haloperidol
• Diazepam
• Desipramine

Topics

• Animals
• Bupropion
• Cocaine (pharmacology)
• Conditioning, Operant (drug effects)
• Cyproheptadine (pharmacology)
• Desipramine (pharmacology)
• Diazepam (pharmacology)
• Dose-Response Relationship, Drug
• Electroshock
• Haloperidol (pharmacology)
• Histamine H1 Antagonists (pharmacology)
• Male
• Propiophenones (pharmacology)
• Saimiri