Clonidine potentiates the effects of tranylcypromine, phenelzine and two analogues in the forced swimming test in mice

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Table 1

Effects of 4 monoamine oxidase (MAO) inhibitors on performance of mice in the forced swimming test

Dose, mg/kg	MAO inhibitor; mean period of immobility (and SEM), s, and % of zero dose

	Tranylcypromine		4-Fluorotranylcypromine		Phenelzine		N²-Acetylphenelzine

0.0	231 (3)	100	233 (2)	100	222 (5)	100	232 (3)	100
0.5	204 (8)	88	228 (3)	98	ND		ND
1.0	223 (4)	97	226 (3)	97	227 (4)	102	237 (1)	102
2.0	214 (12)	93	208 (17)	89	223 (5)	100	220 (10)	95
4.0	191 (15)^*	83	196 (23)	84	232 (3)	104	226 (5)	97
8.0	170 (15)^†	74	192 (13)	82	235 (2)	106	228 (4)	98
16.0	ND		ND		224 (6)	101	228 (4)	98
32.0	ND		ND		231 (4)	104	212 (7)^‡	91
p value^§	0.002		0.104		0.250		0.050

Table 2

Effect of clonidine on anti-immobility effects of the 4 MAO inhibitors

MAO inhibitor; dose, mg/kg	Treatment; mean period of immobility (and SEM), s		% change^†	p value^‡

	Single drug^*	Interaction (clonidine + MAO inhibitor)
TCP				< 0.001
0.0	188 (21)	NA	NA
0.5	204 (12)	163^§ (19)	−17
2.0	214 (12)	133^§^¶ (25)	−35
8.0	170^§ (15)	102^§ (25)	−30
FTCP				< 0.001
0.0	230 (2)	NA	NA
0.5	228 (3)	191^¶ (6)	−16
2.0	208 (17)	173^§^¶ (11)	−15
8.0	191 (13)	129^§^¶ (22)	−27
PLZ				< 0.001
0.0	214 (6)	NA	NA
2.0	223 (5)	170 (22)	−23
8.0	235 (2)	143^§^¶ (21)	−42
32.0	231 (3)	170^¶ (13)	−27
AcPLZ				< 0.001
0.0	214 (6)	NA	NA
2.0	219 (10)	155^§^¶ (20)	−27
8.0	228 (4)	182 (11)	−20
32.0	211 (7)	111^§^¶ (26)	−43

Note: TCP = tranylcypromine, FTCP = 4-fluorotranylcypromine, PLZ = phenelzine, AcPLZ = N²-acetylphenelzine, NA = not applicable.
↵* For zero doses of the 4 MAO inhibitors, the data are for clonidine alone (0.06 mg/kg).
↵† Calculated as (% interaction – % MAO inhibitor alone), where the percentages are calculated with respect to mean periods of immobility (and SEM) for control (vehicle). Mean period of immobility (and SEM) for controls, in seconds: TCP 231 (3), FTCP 223 (2), PLZ 222 (5) and AcPLZ 232 (3).
↵‡ F-test.
↵§ Significantly different from vehicle (p < 0.01) (Sidak’s test, n = 10).
↵¶ Significantly different from MAO inhibitor alone (p < 0.01) (Sidak’s test, n = 10).

Table 3

Effect of lithium on the anti-immobility effects of the 4 MAO inhibitors

MAO inhibitor; dose, mg/kg	Treatment; mean period of immobility (and SEM), s		% change^†

	Single drug^*	Interaction (lithium + MAO inhibitor)
TCP
0.0	218 (4)	NA
0.5	223 (4)	192 (7)	−14
2.0	189 (6)	183 (6)	−3
8.0	155^‡ (14)	165^‡ (15)	+4
FTCP
0.0	230 (3)	NA
0.5	225 (5)	206 (5)	−8
2.0	220 (6)	193^§ (10)	−12
8.0	209 (5)	206 (8)	−1
PLZ
0.0	223 (8)	NA
2.0	227 (4)	224 (5)	−2
8.0	228 (4)	223 (4)	−2
32.0	204^‡ (6)	213 (3)	+4
AcPLZ
0.0	227 (3)	NA
2.0	226 (2)	221 (4)	−2
8.0	226 (4)	226 (3)	0
32.0	207^‡ (6)	204^‡ (7)	−1

↵* For zero doses of the 4 MAO inhibitors, the data are for lithium alone (1 mEq/kg).
↵† Calculated as (% interaction – % MAO inhibitor alone), where the percentages are calculated with respect to mean periods of immobility for control (vehicle). Mean period of immobility (and SEM) for controls, in seconds: TCP 216 (4), FTCP 224 (4), PLZ 228 (4), AcPLZ 231 (1).
↵‡ Significantly different from vehicle (p < 0.01) (Sidak’s test, n = 10).
↵§ Significantly different from vehicle (p < 0.05) (Sidak’s test, n = 10).

Table 4

Effect of quinine on the anti-immobility effects of the 4 MAO inhibitors

MAO inhibitor; dose, mg/kg	Treatment; mean period of immobility (and SEM), s		% change^†

	Single drug^*	Interaction (quinine + MAO inhibitor)
TCP
0.0	217 (4)	NA
0.5	223 (4)	206 (5)	−8
2.0	189 (6)	187 (9)	−1
8.0	155^‡ (14)	178^‡ (10)	+10
FTCP
0.0	227 (3)	NA
0.5	235 (9)	221 (18)	−6
2.0	236 (6)	234 (14)	−1
8.0	222 (23)	216 (22)	−3
PLZ
0.0	231 (3)	NA
2.0	232 (2)	225 (4)	−3
8.0	228 (3)	223 (4)	−2
32.0	227 (4)	226 (4)	0
AcPLZ
0.0	221 (5)	NA
2.0	227 (3)	194^‡ (5)	−15^§
8.0	221 (4)	196^‡ (9)	−11^¶
32.0	223 (3)	178^‡ (6)	−21^§

↵* For zero doses of the 4 MAO inhibitors, the data are for quinine alone (0.5 mg/kg).
↵† Calculated as (% interaction – % MAO inhibitor alone), where the percentages are calculated with respect to mean periods of immobility for control (vehicle). Mean period of immobility (and SEM) for controls, in seconds: TCP 216 (4), FTCP 231 (2), PLZ 231 (3), AcPLZ 221 (5).
↵‡ Significantly different from vehicle (p < 0.01) (Sidak’s test, n = 10).
↵§ Significantly different from AcPLZ alone (p < 0.01) (Sidak’s test, n = 10).
↵¶ Significantly different from AcPLZ alone (p < 0.05) (Sidak’s test, n = 10).