title: Respiratory effects of benzodiazepine-related drugs in awake rhesus monkeys.
abstract: The respiratory effects of several benzodiazepine (BZ) agonists and inverse agonists were compared with those of buspirone and pentobarbital in awake rhesus monkeys. Subjects, fitted with a helmet that served as a pressure displacement plethysmograph, were studied in a ventilated, sound-attenuating chamber; ventilatory frequency, tidal volume (VT) and minute volume (VE) were determined from the plethysmograph signal. During experimental sessions monkeys inhaled either 5% carbon dioxide (CO2) mixed in air or air alone according to a fixed alternating schedule. BZ agonists (alprazolam, 0.01-1.0 mg/kg; lorazepam, 0.3-10.0 mg/kg; quazepam, 1.0-5.6 mg/kg) decreased VT and VE during both 5% CO2 and air inhalation. Pentobarbital (3.0-30.0 mg/kg) also decreased VT and VE and additionally decreased respiratory frequency in monkeys breathing 5% CO2. Two BZ inverse agonists, the beta-carbolines beta-CCE and FG 7142 (0.3-5.6 or 10.00 mg/kg), increased frequency and had no effect on VT, resulting in an increase in VE in monkeys breathing either 5% CO2 or air. The weak BZ inverse agonist CGS 8216 (0.3-5.6 mg/kg) similarly increased ventilation only in monkeys breathing air. Buspirone (0.03-0.3 mg/kg), like the beta-carbolines, increased frequency and VE and, like the BZ agonists, decreased VT. The BZ antagonist Ro15-1788 (0.1-3.0 mg/kg) had little or no effect on ventilation, but Ro15-1788 and also CGS 8216 (both at 1.0 mg/kg) attenuated the respiratory depressant effects of lorazepam or alprazolam. In turn, alprazolam (0.03-0.3 mg/kg) and quazepam (1.0-3.0 mg/kg) attenuated the respiratory stimulant effects of FG 7142.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
authors.forename: J G
authors.initials: JG
authors.lastname: Wettstein
authors.forename: E S
authors.initials: ES
authors.lastname: Teeple
authors.forename: W H
authors.initials: WH
authors.lastname: Morse
mesh_terms: D000280:Administration, Inhalation; D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001067:Appetite Depressants / Q000494:pharmacology; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D008140:Lorazepam / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010991:Plethysmography / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects* / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D001067:Appetite Depressants; D002243:Carbolines; D011720:Pyrazoles; D001569:Benzodiazepines; D002245:Carbon Dioxide; D005442:Flumazenil; C035874:FG 7142; C024915:beta-carboline-3-carboxylic acid ethyl ester; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D010424:Pentobarbital; D008140:Lorazepam; D002065:Buspirone; D000525:Alprazolam